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CitationGPTRetr400

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although previous studies have indicated a high prevalence of ckd and ad among certain groups such as women elderly people those with a low income and those living in rural areas our study created a balanced distribution of demographic and healthrelated factors by matching 15756 individuals with ckd to 63024 participants without ckd Title of the paper: Chronic kidney Disease and the Aging Population. Abstract of the paper: Youth, which is forgiven everything, forgives itself nothing: age, which forgives itself everything, is forgiven nothing. George Bernard Shaw The proportion of older people in the general population is steadily increasing worldwide, with the most rapid growth in low-and middle-income countries [1]. This demographic change is to be celebrated, because it is the consequence of socioeconomic development and better life expectancy. However, population aging also has important implications for society - in diverse areas including health systems, labor markets, public policy, social programs, and family dynamics [2]. A successful response to the aging population will require capitalizing on the opportunities that this transition offers, as well as effectively addressing its challenges. Chronic kidney disease (CKD) is an important public health problem that is characterized by poor health outcomes and very high health care costs. CKD is a major risk multiplier in patients with diabetes, hypertension, heart disease and stroke - all of which are key causes of death and disability in older people [3]. Since the prevalence of CKD is higher in older people, the health impact of population aging will depend in part on how the kidney community responds. March 13, 2014 will mark the celebration of the 9th World Kidney Day (WKD), an annual event jointly sponsored by the International Society of Nephrology and the International Federation of Kidney Foundations. Since its inception in 2006, WKD has become the most successful effort to raise awareness among policymakers and the general public about the importance of kidney disease. The topic for WKD 2014 is "CKD in older people". This article reviews the key links between kidney function, age, health and illness - and discusses the implications of the aging population for the care of people with CKD.

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CitationGPTRetr401

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although previous studies have indicated a high prevalence of ckd and ad among certain groups such as women elderly people those with a low income and those living in rural areas our study created a balanced distribution of demographic and healthrelated factors by matching 15756 individuals with ckd to 63024 participants without ckd Title of the paper: The Prevalence of Renal Failure. Results from the German Health Interview and Examination Survey for Adults, 2008-2011 (DEGS1). Abstract of the paper: BACKGROUND The prevalence of non-end stage renal failure among adults in Germany is unknown. Accurate figures would enable us to estimate the overall need for kidney replacement therapies and the unexploited potential for disease prevention. Renal failure is also an important cardiovascular risk factor. Until now, American prevalence figures have often been applied to Germany despite dissimilarities between the two populations. METHODS We analyzed data on renal function from the nationwide German Health Interview and Examination Survey for Adults, 2008-2011 (DEGS1), which was carried out by the Robert Koch Institute. The glomerular filtration rate was estimated (eGFR) from the serum creatinine and cystatin C levels (CKD-EPI formula) and a semiquantitative measure of albuminuria. Relationships between renal failure and its possible determinants were quantified with adjusted prevalence ratios (PR) and 95% confidence intervals (95% CI). RESULTS Roughly 2.3% (95% CI: [1.9; 2.6 ]) of persons aged 18-79 had an eGFR below 60 mL/min/1.73 m2. The prevalence rose with age. We extrapolated these figures conservatively to persons aged 80 and above, who were not included in the DEGS1, and arrived at a figure of at least 2 million persons in Germany with renal failure. 11.5% of the population have albuminuria of at least 30 mg/L. Diabetes mellitus (PR = 2.25, 95% CI: [1.59; 3.16]) and arterial hypertension (PR = 3.46, 95% CI: [1.95; 6.12]) are important determinants. CONCLUSION This study provides the first representative estimate of the prevalence of renal failure in Germany. The condition is highly dependent on age but less prevalent than previously assumed on the basis of American prevalence figures.

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CitationGPTRetr402

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although previous studies have indicated a high prevalence of ckd and ad among certain groups such as women elderly people those with a low income and those living in rural areas our study created a balanced distribution of demographic and healthrelated factors by matching 15756 individuals with ckd to 63024 participants without ckd Title of the paper: Age affects outcomes in chronic kidney disease. Abstract of the paper: Chronic kidney disease (CKD) is common among the elderly. However, little is known about how the clinical implications of CKD vary with age. We examined the age-specific incidence of death, treated end-stage renal disease (ESRD), and change in estimated glomerular filtration rate (eGFR) among 209,622 US veterans with CKD stages 3 to 5 followed for a mean of 3.2 years. Patients aged 75 years or older at baseline comprised 47% of the overall cohort and accounted for 28% of the 9227 cases of ESRD that occurred during follow-up. Among patients of all ages, rates of both death and ESRD were inversely related to eGFR at baseline. However, among those with comparable levels of eGFR, older patients had higher rates of death and lower rates of ESRD than younger patients. Consequently, the level of eGFR below which the risk of ESRD exceeded the risk of death varied by age, ranging from 45 ml/min per 1.73 m(2) for 18 to 44 year old patients to 15 ml/min per 1.73 m(2) for 65 to 84 year old patients. Among those 85 years or older, the risk of death always exceeded the risk of ESRD in this cohort. Among patients with eGFR levels <45 ml/min per 1.73 m(2) at baseline, older patients were less likely than their younger counterparts to experience an annual decline in eGFR of >3 ml/min per 1.73 m(2). In conclusion, age is a major effect modifier among patients with an eGFR of <60 ml/min per 1.73 m(2), challenging us to move beyond a uniform stage-based approach to managing CKD.

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CitationGPTRetr403

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although previous studies have indicated a high prevalence of ckd and ad among certain groups such as women elderly people those with a low income and those living in rural areas our study created a balanced distribution of demographic and healthrelated factors by matching 15756 individuals with ckd to 63024 participants without ckd Title of the paper: Epidemiology of chronic kidney disease: an update 2022. Abstract of the paper: Chronic kidney disease is a progressive condition that affects >10% of the general population worldwide, amounting to >800 million individuals. Chronic kidney disease is more prevalent in older individuals, women, racial minorities, and in people experiencing diabetes mellitus and hypertension. Chronic kidney disease represents an especially large burden in low- and middle-income countries, which are least equipped to deal with its consequences. Chronic kidney disease has emerged as one of the leading causes of mortality worldwide, and it is one of a small number of non-communicable diseases that have shown an increase in associated deaths over the past 2 decades. The high number of affected individuals and the significant adverse impact of chronic kidney disease should prompt enhanced efforts for better prevention and treatment.

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CitationGPTRetr404

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although previous studies have indicated a high prevalence of ckd and ad among certain groups such as women elderly people those with a low income and those living in rural areas our study created a balanced distribution of demographic and healthrelated factors by matching 15756 individuals with ckd to 63024 participants without ckd Title of the paper: Prevalence of chronic kidney disease in the United States. Abstract of the paper: CONTEXT The prevalence and incidence of kidney failure treated by dialysis and transplantation in the United States have increased from 1988 to 2004. Whether there have been changes in the prevalence of earlier stages of chronic kidney disease (CKD) during this period is uncertain. OBJECTIVE To update the estimated prevalence of CKD in the United States. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional analysis of the most recent National Health and Nutrition Examination Surveys (NHANES 1988-1994 and NHANES 1999-2004), a nationally representative sample of noninstitutionalized adults aged 20 years or older in 1988-1994 (n = 15,488) and 1999-2004 (n = 13,233). MAIN OUTCOME MEASURES Chronic kidney disease prevalence was determined based on persistent albuminuria and decreased estimated glomerular filtration rate (GFR). Persistence of microalbuminuria (>30 mg/g) was estimated from repeat visit data in NHANES 1988-1994. The GFR was estimated using the abbreviated Modification of Diet in Renal Disease Study equation reexpressed to standard serum creatinine. RESULTS The prevalence of both albuminuria and decreased GFR increased from 1988-1994 to 1999-2004. The prevalence of CKD stages 1 to 4 increased from 10.0% (95% confidence interval [CI], 9.2%-10.9%) in 1988-1994 to 13.1% (95% CI, 12.0%-14.1%) in 1999-2004 with a prevalence ratio of 1.3 (95% CI, 1.2-1.4). The prevalence estimates of CKD stages in 1988-1994 and 1999-2004, respectively, were 1.7% (95% CI, 1.3%-2.2%) and 1.8% (95% CI, 1.4%-2.3%) for stage 1; 2.7% (95% CI, 2.2%-3.2%) and 3.2% (95% CI, 2.6%-3.9%) for stage 2; 5.4% (95% CI, 4.9%-6.0%) and 7.7% (95% CI, 7.0%-8.4%) for stage 3; and 0.21% (95% CI, 0.15%-0.27%) and 0.35% (0.25%-0.45%) for stage 4. A higher prevalence of diagnosed diabetes and hypertension and higher body mass index explained the entire increase in prevalence of albuminuria but only part of the increase in the prevalence of decreased GFR. Estimation of GFR from serum creatinine has limited precision and a change in mean serum creatinine accounted for some of the increased prevalence of CKD. CONCLUSIONS The prevalence of CKD in the United States in 1999-2004 is higher than it was in 1988-1994. This increase is partly explained by the increasing prevalence of diabetes and hypertension and raises concerns about future increased incidence of kidney failure and other complications of CKD.

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CitationGPTRetr405

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although previous studies have indicated a high prevalence of ckd and ad among certain groups such as women elderly people those with a low income and those living in rural areas our study created a balanced distribution of demographic and healthrelated factors by matching 15756 individuals with ckd to 63024 participants without ckd Title of the paper: Age and association of kidney measures with mortality and end-stage renal disease. Abstract of the paper: CONTEXT Chronic kidney disease (CKD) is prevalent in older individuals, but the risk implications of low estimated glomerular filtration rate (eGFR) and high albuminuria across the full age range are controversial. OBJECTIVE To evaluate possible effect modification (interaction) by age of the association of eGFR and albuminuria with clinical risk, examining both relative and absolute risks. DESIGN, SETTING, AND PARTICIPANTS Individual-level meta-analysis including 2,051,244 participants from 33 general population or high-risk (of vascular disease) cohorts and 13 CKD cohorts from Asia, Australasia, Europe, and North/South America, conducted in 1972-2011 with a mean follow-up time of 5.8 years (range, 0-31 years). MAIN OUTCOME MEASURES Hazard ratios (HRs) of mortality and end-stage renal disease (ESRD) according to eGFR and albuminuria were meta-analyzed across age categories after adjusting for sex, race, cardiovascular disease, diabetes, systolic blood pressure, cholesterol, body mass index, and smoking. Absolute risks were estimated using HRs and average incidence rates. RESULTS Mortality (112,325 deaths) and ESRD (8411 events) risks were higher at lower eGFR and higher albuminuria in every age category. In general and high-risk cohorts, relative mortality risk for reduced eGFR decreased with increasing age; eg, adjusted HRs at an eGFR of 45 mL/min/1.73 m2 vs 80 mL/min/1.73 m2 were 3.50 (95% CI, 2.55-4.81), 2.21 (95% CI, 2.02-2.41), 1.59 (95% CI, 1.42-1.77), and 1.35 (95% CI, 1.23-1.48) in age categories 18-54, 55-64, 65-74, and ≥75 years, respectively (P <.05 for age interaction). Absolute risk differences for the same comparisons were higher at older age (9.0 [95% CI, 6.0-12.8], 12.2 [95% CI, 10.3-14.3], 13.3 [95% CI, 9.0-18.6], and 27.2 [95% CI, 13.5-45.5] excess deaths per 1000 person-years, respectively). For increased albuminuria, reduction of relative risk with increasing age was less evident, while differences in absolute risk were higher in older age categories (7.5 [95% CI, 4.3-11.9], 12.2 [95% CI, 7.9-17.6], 22.7 [95% CI, 15.3-31.6], and 34.3 [95% CI, 19.5-52.4] excess deaths per 1000 person-years, respectively by age category, at an albumin-creatinine ratio of 300 mg/g vs 10 mg/g). In CKD cohorts, adjusted relative hazards of mortality did not decrease with age. In all cohorts, ESRD relative risks and absolute risk differences at lower eGFR or higher albuminuria were comparable across age categories. CONCLUSIONS Both low eGFR and high albuminuria were independently associated with mortality and ESRD regardless of age across a wide range of populations. Mortality showed lower relative risk but higher absolute risk differences at older age.

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CitationGPTRetr406

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although previous studies have indicated a high prevalence of ckd and ad among certain groups such as women elderly people those with a low income and those living in rural areas our study created a balanced distribution of demographic and healthrelated factors by matching 15756 individuals with ckd to 63024 participants without ckd Title of the paper: Prevalence of depression in chronic kidney disease: systematic review and meta-analysis of observational studies. Abstract of the paper: Prevalence estimates of depression in chronic kidney disease (CKD) vary widely in existing studies. We conducted a systematic review and meta-analysis of observational studies to summarize the point prevalence of depressive symptoms in adults with CKD. We searched MEDLINE and Embase (through January 2012). Random-effects meta-analysis was used to estimate the prevalence of depressive symptoms. We also limited the analyses to studies using clinical interview and prespecified criteria for diagnosis. We included 249 populations (55,982 participants). Estimated prevalence of depression varied by stage of CKD and the tools used for diagnosis. Prevalence of interview-based depression in CKD stage 5D was 22.8% (confidence interval (CI), 18.6-27.6), but estimates were somewhat less precise for CKD stages 1-5 (21.4% (CI, 11.1-37.2)) and for kidney transplant recipients (25.7% (12.8-44.9)). Using self- or clinician-administered rating scales, the prevalence of depressive symptoms for CKD stage 5D was higher (39.3% (CI, 36.8-42.0)) relative to CKD stages 1-5 (26.5% (CI, 18.5-36.5)) and transplant recipients (26.6% (CI, 20.9-33.1)) and suggested that self-report scales may overestimate the presence of depression, particularly in the dialysis setting. Thus, interview-defined depression affects approximately one-quarter of adults with CKD. Given the potential prevalence of depression in the setting of CKD, randomized trials to evaluate effects of interventions for depression on patient-centered outcomes are needed.

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CitationGPTRetr407

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although previous studies have indicated a high prevalence of ckd and ad among certain groups such as women elderly people those with a low income and those living in rural areas our study created a balanced distribution of demographic and healthrelated factors by matching 15756 individuals with ckd to 63024 participants without ckd Title of the paper: Aging and chronic kidney disease: the impact on physical function and cognition. Abstract of the paper: Evidence has recently been building that the presence of chronic kidney disease (CKD) is an independent contributor to decline in physical and cognitive functions in older adults. CKD affects 45% of persons older than 70 years of age and can double the risk for physical impairment, cognitive dysfunction, and frailty. To increase awareness of this relatively new concept of CKD as a risk factor for accelerated aging, we review studies on the association of CKD with physical function, frailty, and cognitive function. We also present a summary of the proposed mechanisms for these associations.

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CitationGPTRetr408

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although previous studies have indicated a high prevalence of ckd and ad among certain groups such as women elderly people those with a low income and those living in rural areas our study created a balanced distribution of demographic and healthrelated factors by matching 15756 individuals with ckd to 63024 participants without ckd Title of the paper: Prevalence of Chronic Kidney Disease in Korea: the Korean National Health and Nutritional Examination Survey 2011-2013. Abstract of the paper: Chronic kidney disease is a leading public health problem related to poor quality of life and premature death. As a resource for evidence-informed health policy-making, we evaluated the prevalence of chronic kidney disease using the data of non-institutionalized adults aged ≥ 20 years (n = 15,319) from the Korean National Health and Nutrition Examination Survey in 2011-2013. Chronic kidney disease was defined as a urine albumin-to-creatinine ratio ≥ 30 mg/g or an estimated glomerular filtration rate < 60 mL/min/1.73 m(2) using the Chronic Kidney Disease-Epidemiology Collaboration equation. The total prevalence estimate of chronic kidney disease for adults aged ≥ 20 years in Korea was 8.2%. By disease stage, the prevalence of chronic kidney disease was as follows: stage 1, 3.0%; stage 2, 2.7%; stage 3a, 1.9%; stage 3b, 0.4%; and stages 4-5, 0.2%. When grouped into three risk categories according to the 2012 Kidney Disease: Improving Global Outcomes guidelines, the proportions for the moderately increased risk, high risk, and very high risk categories were 6.5%, 1.2%, and 0.5%, respectively. Factors including older age, diabetes, hypertension, cardiovascular disease, body mass indexes of ≥ 25 kg/m(2) and < 18.5 kg/m(2), and rural residential area were independently associated with chronic kidney disease. Based on this comprehensive analysis, evidence-based screening strategies for chronic kidney disease in the Korean population should be developed to optimize prevention and early intervention of chronic kidney disease and its associated risk factors.

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CitationGPTRetr409

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although previous studies have indicated a high prevalence of ckd and ad among certain groups such as women elderly people those with a low income and those living in rural areas our study created a balanced distribution of demographic and healthrelated factors by matching 15756 individuals with ckd to 63024 participants without ckd Title of the paper: Epidemiology of cardiovascular disease in chronic renal disease. Abstract of the paper: The risk of cardiovascular disease in patients with chronic renal disease appears to be far greater than in the general population. For example, among patients treated by hemodialysis or peritoneal dialysis, the prevalence of coronary artery disease is approximately 40% and the prevalence of left ventricular hypertrophy is approximately 75%. Cardiovascular mortality has been estimated to be approximately 9% per year. Even after stratification by age, gender, race, and the presence or absence of diabetes, cardiovascular mortality in dialysis patients is 10 to 20 times higher than in the general population. Patients with chronic renal disease should be considered in the highest risk group for subsequent cardiovascular events. Cardiac failure is more common in chronic renal disease patients than in the general population, and is an independent predictor of death in chronic renal disease. Among hemodialysis and peritoneal dialysis patients, the prevalence of cardiac failure is approximately 40%. Both coronary artery disease and left ventricular hypertrophy are risk factors for the development of cardiac failure. In practice, it is difficult to determine whether cardiac failure reflects left ventricular dysfunction or extracellular fluid volume overload. Patients who develop clinical manifestations of cardiac failure should be evaluated for cardiovascular disease.

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CitationGPTRetr410

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although previous studies have indicated a high prevalence of ckd and ad among certain groups such as women elderly people those with a low income and those living in rural areas our study created a balanced distribution of demographic and healthrelated factors by matching 15756 individuals with ckd to 63024 participants without ckd Title of the paper: Analysis of the Global Burden of Disease study highlights the global, regional, and national trends of chronic kidney disease epidemiology from 1990 to 2016. Abstract of the paper: The last quarter century witnessed significant population growth, aging, and major changes in epidemiologic trends, which may have shaped the state of chronic kidney disease (CKD) epidemiology. Here, we used the Global Burden of Disease study data and methodologies to describe the change in burden of CKD from 1990 to 2016 involving incidence, prevalence, death, and disability-adjusted-life-years (DALYs). Globally, the incidence of CKD increased by 89% to 21,328,972 (uncertainty interval 19,100,079- 23,599,380), prevalence increased by 87% to 275,929,799 (uncertainty interval 252,442,316-300,414,224), death due to CKD increased by 98% to 1,186,561 (uncertainty interval 1,150,743-1,236,564), and DALYs increased by 62% to 35,032,384 (uncertainty interval 32,622,073-37,954,350). Measures of burden varied substantially by level of development and geography. Decomposition analyses showed that the increase in CKD DALYs was driven by population growth and aging. Globally and in most Global Burden of Disease study regions, age-standardized DALY rates decreased, except in High-income North America, Central Latin America, Oceania, Southern Sub-Saharan Africa, and Central Asia, where the increased burden of CKD due to diabetes and to a lesser extent CKD due to hypertension and other causes outpaced burden expected by demographic expansion. More of the CKD burden (63%) was in low and lower-middle-income countries. There was an inverse relationship between age-standardized CKD DALY rate and health care access and quality of care. Frontier analyses showed significant opportunities for improvement at all levels of the development spectrum. Thus, the global toll of CKD is significant, rising, and unevenly distributed; it is primarily driven by demographic expansion and in some regions a significant tide of diabetes. Opportunities exist to reduce CKD burden at all levels of development.

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CitationGPTRetr411

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although previous studies have indicated a high prevalence of ckd and ad among certain groups such as women elderly people those with a low income and those living in rural areas our study created a balanced distribution of demographic and healthrelated factors by matching 15756 individuals with ckd to 63024 participants without ckd Title of the paper: Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Abstract of the paper: BACKGROUND Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. METHODS The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. FINDINGS Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, -1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, -1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. INTERPRETATION Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI. FUNDING Bill & Melinda Gates Foundation.

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CitationGPTRetr412

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although previous studies have indicated a high prevalence of ckd and ad among certain groups such as women elderly people those with a low income and those living in rural areas our study created a balanced distribution of demographic and healthrelated factors by matching 15756 individuals with ckd to 63024 participants without ckd Title of the paper: Kidney disease and risk of dementia: a Danish nationwide cohort study. Abstract of the paper: OBJECTIVES It is unclear whether kidney disease is a risk factor for developing dementia. We examined the association between kidney disease and risk of future dementia. DESIGN AND SETTING Nationwide historical registry-based cohort study in Denmark based on data from 1 January 1995 until 31 December 2016. PARTICIPANTS All patients diagnosed with kidney disease and matched general population cohort without kidney disease (matched 1:5 on age, sex and year of kidney disease diagnosis). PRIMARY AND SECONDARY OUTCOME MEASURES All-cause dementia and its subtypes: Alzheimer's disease, vascular dementia and other specified or unspecified dementia. We computed 5-year cumulative incidences (risk) and hazard ratios (HRs) for outcomes using Cox regression analyses. RESULTS The study cohort comprised 82 690 patients with kidney disease and 413 405 individuals from the general population. Five-year and ten-year mortality rates were twice as high in patients with kidney disease compared with the general population. The 5-year risk for all-cause dementia was 2.90% (95% confidence interval: 2.78% to 3.08%) in patients with kidney disease and 2.98% (2.92% to 3.04%) in the general population. Compared with the general population, the adjusted HRs for all-cause dementia in patients with kidney disease were 1.06 (1.00 to 1.12) for the 5-year follow-up and 1.08 (1.03 to 1.12) for the entire study period. Risk estimates for dementia subtypes differed substantially and were lower for Alzheimer's disease and higher for vascular dementia. CONCLUSIONS Patients diagnosed with kidney disease have a modestly increased rate of dementia, mainly driven by vascular dementia. Moreover, patients with kidney disease may be underdiagnosed with dementia due to high mortality and other comorbidities of higher priority.

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CitationGPTRetr413

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although previous studies have indicated a high prevalence of ckd and ad among certain groups such as women elderly people those with a low income and those living in rural areas our study created a balanced distribution of demographic and healthrelated factors by matching 15756 individuals with ckd to 63024 participants without ckd Title of the paper: Chronic kidney disease and cognitive impairment: a systematic review and meta-analysis. Abstract of the paper: BACKGROUND Chronic kidney disease (CKD) has emerged as a possible new risk factor of cognitive impairment and dementia, but results of studies remain conflicting. METHODS A systematic literature research of electronic databases (MEDLINE, Cochrane Library and Goggle Scholar covering the period from 1980 to January 2012) and meta-analysis of relevant cross-sectional and longitudinal studies were conducted to assess the association of CKD and cognitive decline. RESULTS Most cross-sectional and longitudinal studies suggest an association between cognitive impairment and CKD. Meta-analysis of cross-sectional and longitudinal studies comprising 54,779 participants yielded an association of cognitive decline in patients with CKD compared with patients without CKD (OR 1.65, 95% CI 1.32-2.05; p < 0.001, and OR 1.39, 95% CI 1.15-1.68; p < 0.001, respectively). CONCLUSION This is the first meta-analysis assessing the impact of CKD on cognitive decline. Our results suggest CKD being a significant and independent somatic risk factor in the development of cognitive decline.

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CitationGPTRetr414

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although previous studies have indicated a high prevalence of ckd and ad among certain groups such as women elderly people those with a low income and those living in rural areas our study created a balanced distribution of demographic and healthrelated factors by matching 15756 individuals with ckd to 63024 participants without ckd Title of the paper: Worldwide access to treatment for end-stage kidney disease: a systematic review. Abstract of the paper: BACKGROUND End-stage kidney disease is a leading cause of morbidity and mortality worldwide. Prevalence of the disease and worldwide use of renal replacement therapy (RRT) are expected to rise sharply in the next decade. We aimed to quantify estimates of this burden. METHODS We systematically searched Medline for observational studies and renal registries, and contacted national experts to obtain RRT prevalence data. We used Poisson regression to estimate the prevalence of RRT for countries without reported data. We estimated the gap between needed and actual RRT, and projected needs to 2030. FINDINGS In 2010, 2·618 million people received RRT worldwide. We estimated the number of patients needing RRT to be between 4·902 million (95% CI 4·438-5·431 million) in our conservative model and 9·701 million (8·544-11·021 million) in our high-estimate model, suggesting that at least 2·284 million people might have died prematurely because RRT could not be accessed. We noted the largest treatment gaps in low-income countries, particularly Asia (1·907 million people needing but not receiving RRT; conservative model) and Africa (432,000 people; conservative model). Worldwide use of RRT is projected to more than double to 5·439 million (3·899-7·640 million) people by 2030, with the most growth in Asia (0·968 million to a projected 2·162 million [1·571-3·014 million]). INTERPRETATION The large number of people receiving RRT and the substantial number without access to it show the need to both develop low-cost treatments and implement effective population-based prevention strategies. FUNDING Australian National Health and Medical Research Council.

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CitationGPTRetr415

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although previous studies have indicated a high prevalence of ckd and ad among certain groups such as women elderly people those with a low income and those living in rural areas our study created a balanced distribution of demographic and healthrelated factors by matching 15756 individuals with ckd to 63024 participants without ckd Title of the paper: Patients with chronic kidney disease are at an elevated risk of dementia: a population-based cohort study in Taiwan. Abstract of the paper: BACKGROUND Chronic kidney disease (CKD) is more prevalent in Taiwan than in most countries. This population-based cohort study evaluated the dementia risk associated with CKD. METHODS Using claims data of 1,000,000 insured residents covered in the universal health insurance of Taiwan, we selected 37049 adults with CKD newly diagnosed from 2000-2006 as the CKD cohort. We also randomly selected 74098 persons free from CKD and other kidney diseases, frequency matched with age, sex and the date of CKD diagnosed. Incidence and hazard ratios (HRs) of dementia were evaluated by the end of 2009. RESULTS Subjects in the CKD cohort were more prevalent with comorbidities than those in the non-CKD cohort (p <0.0001). The dementia incidence was higher in the CKD cohort than in the non-CKD cohort (9.30 vs. 5.55 per 1,000 person-years), with an overall HR of 1.41 (95% confidence interval (CI), 1.32-1.50), controlling for sex, age, comorbidities and medicaitions. The risk was similar in men and women but increased sharply with age to an HR of 133 (95% CI, 68.9-256) for the elderly. However, the age-specific CKD cohort to non-CKD cohort incidence rate ratio decreased with age, with the highest ratio of 16.0 (95% CI, 2.00-128) in the youngest group. Among comorbidities and medications, alcoholism and taking benzodiazepines were also associated with dementia with elevated adjusted HRs of 3.05 (95% CI 2.17-4.28) and 1.23 (95% CI 1.14-1.32), respectively. CONCLUSIONS Patients with CKD could have an elevated dementia risk. CKD patients with comorbidity deserve attention to prevent dementia.

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CitationGPTRetr416

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although previous studies have indicated a high prevalence of ckd and ad among certain groups such as women elderly people those with a low income and those living in rural areas our study created a balanced distribution of demographic and healthrelated factors by matching 15756 individuals with ckd to 63024 participants without ckd Title of the paper: Racial and ethnic differences in kidney function decline among persons without chronic kidney disease. Abstract of the paper: Whether the rate of kidney function decline before the onset of CKD differs among racial and ethnic groups remains unclear. Here, we evaluated kidney function decline and incident CKD among white, black, Hispanic, and Chinese participants in the Multi-Ethnic Study of Atherosclerosis (MESA) during 5 years of follow-up. We estimated GFR using both cystatin C (eGFRcys) and creatinine (eGFRcreat). The definition of incident CKD required eGFRcys <60 ml/min per 1.73 m(2) and a decline in eGFRcys ≥1 ml/min per year. Among participants with eGFRcreat >60 ml/min per 1.73 m(2) at baseline, blacks had a significantly higher rate of kidney function decline than whites (0.31 ml/min per 1.73 m(2)/yr faster on average, P=0.001), even after adjusting for multiple potential confounders. Among Hispanics, Dominicans and Puerto Ricans had faster rates of decline than whites (0.55 and 0.47 ml/min per 1.73 m(2)/yr faster, respectively). Mexicans, South Americans, or other Hispanics had similar rates of decline compared to whites. We did not detect significant differences in the rates of kidney function decline among Chinese and white participants. Among those with normal or near-normal kidney function at baseline, blacks and Hispanics had the highest rates of incident CKD during follow-up. Adjustment for comorbidities attenuated some of these differences. In conclusion, the average rate of kidney function decline before the onset of CKD differs among racial and ethnic groups. Traditional risk factors do not explain these differences fully, highlighting the need to explore these disparities.

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CitationGPTRetr417

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although previous studies have indicated a high prevalence of ckd and ad among certain groups such as women elderly people those with a low income and those living in rural areas our study created a balanced distribution of demographic and healthrelated factors by matching 15756 individuals with ckd to 63024 participants without ckd Title of the paper: Prevalence of chronic diseases and multimorbidity among the elderly population in Sweden. Abstract of the paper: We explored the role of age, gender, and socioeconomic status in the occurrence of chronic diseases and multimorbidity in 1099 elderly participants in the Kungsholmen Project. Cardiovascular and mental diseases were the most common chronic disorders. Of the participants, 55% had multimorbidity. Advanced age, female gender, and lower education were independently associated with a more than 50% increased risk for multimorbidity. Multimorbidity is the most common clinical picture of the elderly and may be increased by unhealthy behaviors linked to education.

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CitationGPTRetr418

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although previous studies have indicated a high prevalence of ckd and ad among certain groups such as women elderly people those with a low income and those living in rural areas our study created a balanced distribution of demographic and healthrelated factors by matching 15756 individuals with ckd to 63024 participants without ckd Title of the paper: High prevalence of stage 3 chronic kidney disease in older adults despite normal serum creatinine. Abstract of the paper: BACKGROUND Serum creatinine is commonly used to diagnose chronic kidney disease (CKD), but may underestimate CKD in older adults when compared with using glomerular filtration rates (eGFR). The magnitude of this underestimation is not clearly defined. OBJECTIVE Using the Modification of Diet in Renal Disease (MDRD) equation, to describe both the prevalence and the magnitude of underestimation of stage 3 CKD (GFR 30-59 ml/min/1.73 m(2)), as well as ideal serum creatinine cutoff values to diagnose stage 3 CKD among Americans > or =65 years of age. DESIGN Cross-sectional. PARTICIPANTS A total of 3,406 participants > or =65 years of age from the 1999-2004 National Health and Nutrition Examination Surveys (NHANES). MEASUREMENTS Serum creatinine levels were used to determine eGFR from the MDRD equation. Information on clinical conditions was self-reported. RESULTS Overall, 36.1% of older adults in the US have stage 3 or greater CKD as defined by eGFR values. Among older adults with stage 3 CKD, 80.6% had creatinine values < or =1.5 mg/dl, and 38.6% had creatinine values < or =1.2 mg/dl. Optimal cutoff values for serum creatinine in the diagnosis of stage 3 CKD in older adults were > or =1.3 mg/dl for men and > or =1.0 mg/dl for women, regardless of the presence or absence of hypertension, diabetes, or congestive heart failure. CONCLUSION Use of serum creatinine underestimates the presence of advanced (stage 3 or greater) CKD among older adults in the US. Automated eGFR reporting may improve the accuracy of risk stratification for older adults with CKD.

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CitationGPTRetr419

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although previous studies have indicated a high prevalence of ckd and ad among certain groups such as women elderly people those with a low income and those living in rural areas our study created a balanced distribution of demographic and healthrelated factors by matching 15756 individuals with ckd to 63024 participants without ckd Title of the paper: Cognitive function in chronic kidney disease. Abstract of the paper: Chronic kidney disease (CKD) is a growing public health problem. The incidence of kidney failure is rising in all age groups but particularly in older adults. Individuals in all stages of CKD are at higher risk for development of cognitive impairment and this may be a major determinant in their quality of life. Furthermore, cognitive impairment is associated with an increased risk of death in dialysis patients. Cerebrovascular disease is a strong risk factor for development of cognitive impairment and vascular disease is a more likely cause of cognitive impairment than Alzheimer's disease in patients with CKD. Both traditional and nontraditional vascular risk factors are more common in CKD and dialysis patients may also be at risk for cognitive impairment via nonvascular risk factors and the hemodialysis procedure itself. Unfortunately, because risk factors for cognitive impairment in CKD have not been thoroughly ascertained, evaluation of potential treatments has been limited. Given the high prevalence of cognitive impairment in all stages of CKD, additional studies are needed to evaluate potential risk factors and treatments in this vulnerable population.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although most previous research focused on tau phosphosites as potential biomarkers or therapeutic targets some recent works highlighted the importance of other types of ptms in tauopathies as ubiquitination or acetylation Title of the paper: Analysis of post-translational modifications in Alzheimer's disease by mass spectrometry. Abstract of the paper: The roles of post-translational modifications (PTMs) in the onset and progression of disease have been extensively studied for decades. More specifically, various PTMs have been the focus of research in Alzheimer's disease (AD). The two most discussed hallmarks of the disease, senile plaques and tau tangles, are the result of PTMs of the amyloidβ protein precursor (AβPP) and the microtubule stabilizing protein: tau. While these modifications have been characterized indirectly by biochemical-based methods, the primary shortcoming to this research can be linked to a lack of a thorough molecular-based means of qualitative and quantitative analysis of many of these modifications within transgenic animal, and human samples. In this review, we discuss the important proteins and their associated PTMs linked to AD and the ways in which mass spectrometry has and will be utilized to analyze them. We also comment on novel ways in which molecular-based mass spectrometry methods should be employed going forward to resolve the interconnections of the PTMs involvement in various stages of AD pathology (preclinical, mild cognitive impairment, advanced-stage AD).

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although most previous research focused on tau phosphosites as potential biomarkers or therapeutic targets some recent works highlighted the importance of other types of ptms in tauopathies as ubiquitination or acetylation Title of the paper: Post-translational modifications of tau protein in Alzheimer's disease. Abstract of the paper: Microtubule-associated protein tau undergoes several post-translational modifications and aggregates into paired helical filaments (PHFs) in Alzheimer's disease (AD) and other tauopathies. These modifications of tau include hyperphosphorylation, glycosylation, ubiquitination, glycation, polyamination, nitration, and proteolysis. Hyperphosphorylation and glycosylation are crucial to the molecular pathogenesis of neurofibrillary degeneration of AD. The others appear to represent failed mechanisms for neurons to remove damaged, misfolded, and aggregated proteins. This review summarizes the abnormal post-translational modifications of tau and discusses the pathophysiological relevance of hyperphosphorylation and glycosylation of tau. Total tau and phosphorylated tau levels in cerebrospinal fluid as a diagnostic biomarkers are also reviewed. Analyses of the current advances in tau modifications suggest that intervention addressing these abnormalities may offer promising therapeutic opportunities to prevent and treat neurofibrillary degeneration of AD and other tauopathies.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although most previous research focused on tau phosphosites as potential biomarkers or therapeutic targets some recent works highlighted the importance of other types of ptms in tauopathies as ubiquitination or acetylation Title of the paper: Post-translational modifications of tau protein: implications for Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) belongs to a group of neurodegenerative diseases collectively designated as "tauopathies", because they are characterized by the aggregation of abnormally phosphorylated tau protein. The mechanisms responsible for tau aggregation and its contribution to neurodegeneration are still unknown. Thereby, understanding the modes of regulation of tau is of high interest in the determination of the possible causes at the origin of the formation of tau aggregates and to elaborate protection strategies to cope with these pathological lesions. The regulation of tau takes place predominantly through post-translational modifications. Extensive reports have been published about tau phosphorylation; however, the other tau post-translational modifications have received much less attention. Here, we review the different types of post-translational modifications of tau including phosphorylation, glycosylation, glycation, prolyl-isomerization, cleavage or truncation, nitration, polyamination, ubiquitination, sumoylation, oxidation and aggregation, with a particular interest towards their relevance in AD.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although most previous research focused on tau phosphosites as potential biomarkers or therapeutic targets some recent works highlighted the importance of other types of ptms in tauopathies as ubiquitination or acetylation Title of the paper: Acetylation: a new key to unlock tau's role in neurodegeneration. Abstract of the paper: The identification of tau protein as a major constituent of neurofibrillary tangles spurred considerable effort devoted to identifying and validating pathways through which therapeutics may alleviate tau burden in Alzheimer's disease and related tauopathies, including chronic traumatic encephalopathy associated with sport- and military-related injuries. Most tau-based therapeutic strategies have previously focused on modulating tau phosphorylation, given that tau species present within neurofibrillary tangles are hyperphosphorylated on a number of different residues. However, the recent discovery that tau is modified by acetylation necessitates additional research to provide greater mechanistic insight into the spectrum of physiological consequences of tau acetylation, which may hold promise as a novel therapeutic target. In this review, we discuss recent findings evaluating tau acetylation in the context of previously accepted notions regarding tau biology and pathophysiology. We also examine the evidence demonstrating the neuroprotective and beneficial consequences of inhibiting histone deacetylase (HDAC)6, a tau deacetylase, including its effect on microtubule stabilization. We also discuss the rationale for pharmacologically modulating HDAC6 in tau-based pathologies as a novel therapeutic strategy.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although most previous research focused on tau phosphosites as potential biomarkers or therapeutic targets some recent works highlighted the importance of other types of ptms in tauopathies as ubiquitination or acetylation Title of the paper: The Involvement of Post-Translational Modifications in Alzheimer's Disease. Abstract of the paper: BACKGROUND Alzheimer's disease (AD) is a neurodegenerative disorder recognized as the most common cause of chronic dementia among the ageing population. AD is histopathologically characterized by progressive loss of neurons and deposits of insoluble proteins, primarily composed of amyloid-β pelaques and neurofibrillary tangles (NFTs). METHODS Several molecular processes contribute to the formation of AD cellular hallmarks. Among them, post-translational modifications (PTMs) represent an attractive mechanism underlying the formation of covalent bonds between chemical groups/peptides to target proteins, which ultimately result modified in their function. Most of the proteins related to AD undergo PTMs. Several recent studies show that AD-related proteins like APP, Aβ, tau, BACE1 undergo post-translational modifications. The effect of PTMs contributes to the normal function of cells, although aberrant protein modification, which may depend on many factors, can drive the onset or support the development of AD. RESULTS Here we will discuss the effect of several PTMs on the functionality of AD-related proteins potentially contributing to the development of AD pathology. CONCLUSION We will consider the role of Ubiquitination, Phosphorylation, SUMOylation, Acetylation and Nitrosylation on specific AD-related proteins and, more interestingly, the possible interactions that may occur between such different PTMs.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although most previous research focused on tau phosphosites as potential biomarkers or therapeutic targets some recent works highlighted the importance of other types of ptms in tauopathies as ubiquitination or acetylation Title of the paper: A current view on Tau protein phosphorylation in Alzheimer's disease. Abstract of the paper: The functions of the neuronal microtubule-associated protein Tau in the central nervous system are regulated by manifold posttranslational modifications at more than 50 sites. Tau in healthy neurons carries multiple phosphate groups, mostly in its microtubule assembly domain. Elevated phosphorylation and aggregation of Tau are widely considered pathological hallmarks in Alzheimer's disease (AD) and other tauopathies, triggering the quest for Tau posttranslational modifications in the disease context. However, the phosphorylation patterns of physiological and pathological Tau are surprisingly similar and heterogenous, making it difficult to identify specific modifications as therapeutic targets and biomarkers for AD. We present a concise summary of - and view on - important previous and recent advances in Tau phosphorylation analysis in the context of AD.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although most previous research focused on tau phosphosites as potential biomarkers or therapeutic targets some recent works highlighted the importance of other types of ptms in tauopathies as ubiquitination or acetylation Title of the paper: The role of tau kinases in Alzheimer's disease. Abstract of the paper: A principal feature of the progression of Alzheimer's disease (AD) is the appearance of aberrant phosphorylation of the microtubule-associated protein tau in the brains of affected individuals. Significant research efforts have been directed at identifying the kinases involved in this process, as well as developing pharmacological agents to inhibit these molecules. This review focuses on recent developments in both the physiological and pathological effects of tau phosphorylation, and the contribution of phosphorylation to tau toxicity and pathological progression in AD. The evolving concepts of the roles tau plays in cellular biology, and the mechanisms by which phosphorylation regulates tau function, is reshaping the framework for the development of therapeutics targeting tau to treat AD.

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CitationGPTRetr427

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although most previous research focused on tau phosphosites as potential biomarkers or therapeutic targets some recent works highlighted the importance of other types of ptms in tauopathies as ubiquitination or acetylation Title of the paper: Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer's Disease. Abstract of the paper: To elucidate the role of Tau isoforms and post-translational modification (PTM) stoichiometry in Alzheimer's disease (AD), we generated a high-resolution quantitative proteomics map of 95 PTMs on multiple isoforms of Tau isolated from postmortem human tissue from 49 AD and 42 control subjects. Although Tau PTM maps reveal heterogeneity across subjects, a subset of PTMs display high occupancy and frequency for AD, suggesting importance in disease. Unsupervised analyses indicate that PTMs occur in an ordered manner, leading to Tau aggregation. The processive addition and minimal set of PTMs associated with seeding activity was further defined by analysis of size-fractionated Tau. To summarize, features in the Tau protein critical for disease intervention at different stages of disease are identified, including enrichment of 0N and 4R isoforms, underrepresentation of the C terminus, an increase in negative charge in the proline-rich region (PRR), and a decrease in positive charge in the microtubule binding domain (MBD).

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although most previous research focused on tau phosphosites as potential biomarkers or therapeutic targets some recent works highlighted the importance of other types of ptms in tauopathies as ubiquitination or acetylation Title of the paper: Degradation or aggregation: the ramifications of post-translational modifications on tau. Abstract of the paper: Tau protein is encoded in the microtubule-associated protein tau (MAPT) gene and contributes to the stability of microtubules in axons. Despite of its basic isoelectric point and high solubility, tau is often found in intraneuronal filamentous inclusions such as paired helical filaments (PHFs), which are the primary constituent of neurofibrillary tangles (NFTs). This pathological feature is the nosological entity termed "tauopathies" which notably include Alzheimer's disease (AD). A proteinaceous signature of all tauopathies is hyperphosphorylation of the accumulated tau, which has been extensively studied as a major pharmacological target for AD therapy. However, in addition to phosphorylation events, tau undergoes a number of diverse posttranslational modifications (PTMs) which appear to be controlled by complex crosstalk. It remains to be elucidated which of the PTMs or their combinations have pro-aggregation or anti-aggregation properties. In this review, we outline the consequences of and communications between several key PTMs of tau, such as acetylation, phosphorylation, and ubiquitination, focusing on their roles in aggregation and degradation. We place emphasis on the structure of tau protofilaments from the human AD brain, which may be good targets to modulate etiological PTMs which cause tau aggregation. [BMB Reports 2018; 51(6): 265-273].

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CitationGPTRetr429

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although most previous research focused on tau phosphosites as potential biomarkers or therapeutic targets some recent works highlighted the importance of other types of ptms in tauopathies as ubiquitination or acetylation Title of the paper: "Don't Phos Over Tau": recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimer's disease and other tauopathies. Abstract of the paper: Phosphorylation is one of the most prevalent post-translational modifications found in aggregated tau isolated from Alzheimer's disease (AD) patient brains. In tauopathies like AD, increased phosphorylation or hyperphosphorylation can contribute to microtubule dysfunction and is associated with tau aggregation. In this review, we provide an overview of the structure and functions of tau protein as well as the physiologic roles of tau phosphorylation. We also extensively survey tau phosphorylation sites identified in brain tissue and cerebrospinal fluid from AD patients compared to age-matched healthy controls, which may serve as disease-specific biomarkers. Recently, new assays have been developed to measure minute amounts of specific forms of phosphorylated tau in both cerebrospinal fluid and plasma, which could potentially be useful for aiding clinical diagnosis and monitoring disease progression. Additionally, multiple therapies targeting phosphorylated tau are in various stages of clinical trials including kinase inhibitors, phosphatase activators, and tau immunotherapy. With promising early results, therapies that target phosphorylated tau  could be useful at slowing tau hyperphosphorylation and aggregation in AD and other tauopathies.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although most previous research focused on tau phosphosites as potential biomarkers or therapeutic targets some recent works highlighted the importance of other types of ptms in tauopathies as ubiquitination or acetylation Title of the paper: Acetylation unleashes protein demons of dementia. Abstract of the paper: Aberrant posttranslational modifications of proteins can impair synaptic plasticity and may render neurons vulnerable to degeneration during aging. In this issue of Neuron, Min et al. show that acetylation of the amino acid lysine in the microtubule-associated protein tau prevents its ubiquitin-mediated degradation, resulting in "tau tangles" similar to those of dementias. Other recent studies suggest that lysine hyperacetylation contributes to the accumulation of amyloid β-peptide in Alzheimer's disease and to impaired cognitive function resulting from a trophic factor deficit.

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CitationGPTRetr431

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although most previous research focused on tau phosphosites as potential biomarkers or therapeutic targets some recent works highlighted the importance of other types of ptms in tauopathies as ubiquitination or acetylation Title of the paper: Tau phosphorylation: the therapeutic challenge for neurodegenerative disease. Abstract of the paper: The microtubule-associated protein tau is integral to the pathogenesis of Alzheimer's disease (AD), as well as several related disorders, termed tauopathies, in which tau is deposited in affected brain regions. In the tauopathies, pathological tau is in an elevated state of phosphorylation and is aberrantly cleaved. It also exhibits abnormal conformations and becomes aggregated, resulting in neurofibrillary tau pathology. Recent evidence suggests that relatively early disease-associated changes in soluble tau proteins, including phosphorylation, are involved in the induction of neuronal death. Here, we summarize recent developments that suggest new therapeutic strategies to prevent or reduce the progression of pathology in the tauopathies. A list of tau phosphorylation sites identified in the tauopathies and in controls accompanies this review.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although most previous research focused on tau phosphosites as potential biomarkers or therapeutic targets some recent works highlighted the importance of other types of ptms in tauopathies as ubiquitination or acetylation Title of the paper: A Closer Look into the Role of Protein Tau in the Identification of Promising Therapeutic Targets for Alzheimer's Disease. Abstract of the paper: One of the most commonly known chronic neurodegenerative disorders, Alzheimer's disease (AD), manifests the common type of dementia in 60⁻80% of cases. From a clinical standpoint, a patent cognitive decline and a severe change in personality, as caused by a loss of neurons, is usually evident in AD with about 50 million people affected in 2016. The disease progression in patients is distinguished by a gradual plummet in cognitive functions, eliciting symptoms such as memory loss, and eventually requiring full-time medical care. From a histopathological standpoint, the defining characteristics are intracellular aggregations of hyper-phosphorylated tau protein, known as neurofibrillary tangles (NFT), and depositions of amyloid β-peptides (Aβ) in the brain. The abnormal phosphorylation of tau protein is attributed to a wide gamut of neurological disorders known as tauopathies. In addition to the hyperphosphorylated tau lesions, neuroinflammatory processes could occur in a sustained manner through astro-glial activation, resulting in the disease progression. Recent findings have suggested a strong interplay between the mechanism of Tau phosphorylation, disruption of microtubules, and synaptic loss and pathology of AD. The mechanisms underlying these interactions along with their respective consequences in Tau pathology are still ill-defined. Thus, in this review: (1) we highlight the interplays existing between Tau pathology and AD; and (2) take a closer look into its role while identifying some promising therapeutic advances including state of the art imaging techniques.

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CitationGPTRetr433

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although most previous research focused on tau phosphosites as potential biomarkers or therapeutic targets some recent works highlighted the importance of other types of ptms in tauopathies as ubiquitination or acetylation Title of the paper: Tau and neurodegenerative disorders. Abstract of the paper: The mechanisms that render tau a toxic agent are still unclear, although increasing evidence supports the assertion that alterations of tau can directly cause neuronal degeneration. In addition, it is unclear whether neurodegeneration in various tauopathies occurs via a common mechanism or that specific differences exist. The aim of this review is to provide an overview of tauopathies from bench to bedside. The review begins with clinicopathological findings of familial and sporadic tauopathies. It includes a discussion of the similarities and differences between these two conditions. The second part concentrates on biochemical alterations of tau such as phosphorylation, truncation and acetylation. Although pathological phosphorylation of tau has been studied for many years, recently researchers have focused on the physiological role of tau during development. Finally, the review contains a summary of the significance of tauopathy model mice for research on neurofibrillary tangles, axonopathies, and synaptic alteration.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although most previous research focused on tau phosphosites as potential biomarkers or therapeutic targets some recent works highlighted the importance of other types of ptms in tauopathies as ubiquitination or acetylation Title of the paper: Post-translational modifications of tau protein. Abstract of the paper: Microtubule-associated protein tau is a phosphoprotein whose expression and phosphorylation is developmentally regulated. Whereas in adult mammalian brain several isoforms are produced from a single gene by alternative splicing, in fetal brain only a single isoform exists, corresponding to the smallest of the tau isoforms. Main physiological function of tau is the promotion of assembly and stabilization of microtubular network, which is essential for normal axonal transport of vesicles within the neuron. In human, tau protein undergoes several posttranslational modifications: such as phosphorylation, truncation, nitration, glycation, glycosylation, ubiquitination and polyaminations. When these modifications are disturbed, they play a serious role during the pathogenesis of Alzheimer's disease (AD). Hyperphosphorylation and truncation as the early events in AD pathogenesis, play significant role in the formation of neurofibrillary pathology. Phosphorylated tau has reduced capability in binding to microtubules and hyperphosphorylation together with truncation contributes to the formation of pathological tau filaments. This leads to destabilization of microtubular network and subsequent impairment of microtubule associated axonal transport. Since many data suggest that sporadic AD is the "disease of posttranslational modifications" of tau protein, more detailed investigation of tau protein modifications is urgently needed in order to understand pathogenesis of sporadic Alzheimer's disease (Fig. 1, Ref. 86).

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although most previous research focused on tau phosphosites as potential biomarkers or therapeutic targets some recent works highlighted the importance of other types of ptms in tauopathies as ubiquitination or acetylation Title of the paper: Alzheimer's disease: phenotypic approaches using disease models and the targeting of tau protein. Abstract of the paper: Introduction: Hyperphosphorylated and aggregated tau protein is the main hallmark of a class of neurodegenerative disorders known as tauopathies. Tau is a microtubule-binding protein which is important for microtubule assembly and stabilization, for proper axonal transport and overall neuronal integrity. However, in tauopathies, tau undergoes aberrant post-translational modifications that fundamentally affect its normal function. The etiology of these devastating diseases is unclear and there is no treatment for these disorders.Areas covered: This review examines the neurobiology of tau, tau post-translational modifications, and tau pathophysiology. Progress regarding the effort to identify and assess novel tau-targeted therapeutic strategies in preclinical studies is also discussed. We performed a search on PubMed of the relevant literature published between 1995 and 2020.Expert opinion: Tau diversity and the lack of clinically available test to diagnose and identify tauopathies are major obstacles; they represent a possible reason for the lack of success of clinical trials. However, given the encouraging advances in PET tau imaging and tau neurobiology, we believe that a more personalized approach could be on the horizon and that this will be key to addressing the heterogeneity of tau pathology.

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CitationGPTRetr436

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although most previous research focused on tau phosphosites as potential biomarkers or therapeutic targets some recent works highlighted the importance of other types of ptms in tauopathies as ubiquitination or acetylation Title of the paper: Methylation as a key regulator of Tau aggregation and neuronal health in Alzheimer's disease. Abstract of the paper: Neurodegenerative diseases like Alzheimer's, Parkinson's and Huntington's disease involves abnormal aggregation and accumulation of toxic proteins aggregates. Post-translational modifications (PTMs) of the causative proteins play an important role in the etiology of disease as they could either slow down or accelerate the disease progression. Alzheimer disease is associated with the aggregation and accumulation of two major protein aggregates-intracellular neurofibrillary tangles made up of microtubule-associated protein Tau and extracellular Amyloid-β plaques. Post-translational modifications are important for the regulation of Tau`s function but an imbalance in PTMs may lead to abnormal Tau function and aggregation. Tau methylation is one of the important PTM of Tau in its physiological state. However, the methylation signature on Tau lysine changes once it acquires pathological aggregated form. Tau methylation can compete with other PTMs such as acetylation and ubiquitination. The state of PTM at these sites determines the fate of Tau protein in terms of its function and stability. The global methylation in neurons, microglia and astrocytes are involved in multiple cellular functions involving their role in epigenetic regulation of gene expression via DNA methylation. Here, we have discussed the effect of methylation on Tau function in a site-specific manner and their cross-talk with other lysine modifications. We have also elaborated the role of methylation in epigenetic aspects and neurodegenerative conditions associated with the imbalance in methylation metabolism affecting global methylation state of cells. Video abstract.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although most previous research focused on tau phosphosites as potential biomarkers or therapeutic targets some recent works highlighted the importance of other types of ptms in tauopathies as ubiquitination or acetylation Title of the paper: Animal models reveal role for tau phosphorylation in human disease. Abstract of the paper: Many proteins that are implicated in human disease are posttranslationally modified. This includes the microtubule-associated protein tau that is deposited in a hyperphosphorylated form in brains of Alzheimer's disease patients. The focus of this review article is on the physiological and pathological phosphorylation of tau; the relevance of aberrant phosphorylation for disease; the role of kinases and phosphatases in this process; its modeling in transgenic mice, flies, and worms; and implications of phosphorylation for therapeutic intervention.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although most previous research focused on tau phosphosites as potential biomarkers or therapeutic targets some recent works highlighted the importance of other types of ptms in tauopathies as ubiquitination or acetylation Title of the paper: Acetylation of tau inhibits its degradation and contributes to tauopathy. Abstract of the paper: Neurodegenerative tauopathies characterized by hyperphosphorylated tau include frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17) and Alzheimer's disease (AD). Reducing tau levels improves cognitive function in mouse models of AD and FTDP-17, but the mechanisms regulating the turnover of pathogenic tau are unknown. We found that tau is acetylated and that tau acetylation prevents degradation of phosphorylated tau (p-tau). We generated two antibodies specific for acetylated tau and showed that tau acetylation is elevated in patients at early and moderate Braak stages of tauopathy. Histone acetyltransferase p300 was involved in tau acetylation and the class III protein deacetylase SIRT1 in deacetylation. Deleting SIRT1 enhanced levels of acetylated-tau and pathogenic forms of p-tau, probably by blocking proteasome-mediated degradation. Inhibiting p300 with a small molecule promoted tau deacetylation and eliminated p-tau associated with tauopathy. Modulating tau acetylation could be a new therapeutic strategy to reduce tau-mediated neurodegeneration.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: although most previous research focused on tau phosphosites as potential biomarkers or therapeutic targets some recent works highlighted the importance of other types of ptms in tauopathies as ubiquitination or acetylation Title of the paper: The importance of tau phosphorylation for neurodegenerative diseases. Abstract of the paper: Fibrillar deposits of highly phosphorylated tau are a key pathological feature of several neurodegenerative tauopathies including Alzheimer's disease (AD) and some frontotemporal dementias. Increasing evidence suggests that the presence of these end-stage neurofibrillary lesions do not cause neuronal loss, but rather that alterations to soluble tau proteins induce neurodegeneration. In particular, aberrant tau phosphorylation is acknowledged to be a key disease process, influencing tau structure, distribution, and function in neurons. Although typically described as a cytosolic protein that associates with microtubules and regulates axonal transport, several additional functions of tau have recently been demonstrated, including roles in DNA stabilization, and synaptic function. Most recently, studies examining the trans-synaptic spread of tau pathology in disease models have suggested a potential role for extracellular tau in cell signaling pathways intrinsic to neurodegeneration. Here we review the evidence showing that tau phosphorylation plays a key role in neurodegenerative tauopathies. We also comment on the tractability of altering phosphorylation-dependent tau functions for therapeutic intervention in AD and related disorders.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: data obtained from janelidze et al majbour olsson et al suárezcalvet and wellington et al Title of the paper: CSF biomarkers for the differential diagnosis of Alzheimer's disease: A large-scale international multicenter study. Abstract of the paper: INTRODUCTION The aim of this study was to test the diagnostic value of cerebrospinal fluid (CSF) beta-amyloid (Aβ1-42), phosphorylated tau, and total tau (tau) to discriminate Alzheimer's disease (AD) dementia from other forms of dementia. METHODS A total of 675 CSF samples collected at eight memory clinics were obtained from healthy controls, AD dementia, subjective memory impairment, mild cognitive impairment, vascular dementia, Lewy body dementia (LBD), fronto-temporal dementia (FTD), depression, or other neurological diseases. RESULTS CSF Aβ1-42 showed the best diagnostic accuracy among the CSF biomarkers. At a sensitivity of 85%, the specificity to differentiate AD dementia against other diagnoses ranged from 42% (for LBD, 95% confidence interval or CI = 32-62) to 77% (for FTD, 95% CI = 62-90). DISCUSSION CSF Aβ1-42 discriminates AD dementia from FTD, but shows significant overlap with other non-AD forms of dementia, possibly reflecting the underlying mixed pathologies.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: data obtained from janelidze et al majbour olsson et al suárezcalvet and wellington et al Title of the paper: Advantages and disadvantages of the use of the CSF Amyloid β (Aβ) 42/40 ratio in the diagnosis of Alzheimer's Disease. Abstract of the paper: The cerebrospinal fluid (CSF) biochemical markers (biomarkers) Amyloidβ 42 (Aβ42), total Tau (T-tau) and Tau phosphorylated at threonine 181 (P-tau181) have proven diagnostic accuracy for mild cognitive impairment and dementia due to Alzheimer's Disease (AD). In an effort to improve the accuracy of an AD diagnosis, it is important to be able to distinguish between AD and other types of dementia (non-AD). The concentration ratio of Aβ42 to Aβ40 (Aβ42/40 Ratio) has been suggested to be superior to the concentration of Aβ42 alone when identifying patients with AD. This article reviews the available evidence on the use of the CSF Aβ42/40 ratio in the diagnosis of AD. Based on the body of evidence presented herein, it is the conclusion of the current working group that the CSF Aβ42/40 ratio, rather than the absolute value of CSF Aβ42, should be used when analysing CSF AD biomarkers to improve the percentage of appropriately diagnosed patients.

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CitationGPTRetr442

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: data obtained from janelidze et al majbour olsson et al suárezcalvet and wellington et al Title of the paper: CSF biomarkers for Alzheimer's disease: current utility and potential future use. Abstract of the paper: Over the past 15 years, cerebrospinal fluid (CSF) biomarkers have been shown to be useful for both the diagnosis as well as the prognosis in Alzheimer's disease. It has been shown the CSF levels of amyloid-β (Aβ)(42) are a very good marker for the presence of amyloid deposition in the brain regardless of clinical status and that total tau and phosphorylated forms of tau are useful in detection of neurodegeneration. When combined together, these CSF markers are useful not only in differential diagnosis but also in predicting conversion and rate of progression from mild cognitive impairment/very mild dementia to more severe impairment. The markers are also useful in predicting conversion from cognitive normalcy to very mild dementia. This field is briefly reviewed and recommendations for future studies in this area are provided.

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CitationGPTRetr443

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: data obtained from janelidze et al majbour olsson et al suárezcalvet and wellington et al Title of the paper: CSF biomarkers for Alzheimer's Disease: levels of beta-amyloid, tau, phosphorylated tau relate to clinical symptoms and survival. Abstract of the paper: UNLABELLED Cerebrospinal fluid (CSF) samples from 21 patients with a clinical diagnosis of Alzheimer's disease (AD) participating in a 5-year treatment study with the choline esterase inhibitor tacrin were retrospectively analyzed for the contents of beta-amyloid (Abeta42), total tau (T-tau) and phosphorylated tau (P-tau). A significant positive correlation between the level of P-tau and the number of symptoms according to the DSM-IV criteria (p = 0.041) and the NINCDS-ADRDA (p = 0.029) was observed (i.e. higher levels were found in cases with more symptoms). A significant positive correlation between T-tau, P-tau and ADAS-cog score was identified (i.e. higher levels were found with more severe cognitive dysfunction). Patients who died during the 5-year follow-up had significantly lower levels of Abeta42 (p = 0.011) than those who were still alive. Patients who had died in a 6-year follow-up had significantly lower levels of Abeta42 (p = 0.034) and higher levels of T-tau (p = 0.041) than patients still alive. CONCLUSION CSF biomarkers do aid the clinical diagnosis of AD. Increased levels of P-tau and T-tau are possible markers for severity and abundance of symptoms in AD. Low levels of Abeta42 may indicate a higher risk of early death in AD.

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CitationGPTRetr444

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: data obtained from janelidze et al majbour olsson et al suárezcalvet and wellington et al Title of the paper: Cerebrospinal Fluid Biomarkers in Alzheimer's Disease: An Invaluable Tool for Clinical Diagnosis and Trial Enrichment. Abstract of the paper: Alzheimer's disease (AD) is the most common neurodegenerative disorder, affecting around 35 million people worldwide. Cerebrospinal fluid (CSF) biomarkers entered the diagnostic criteria as support for early diagnosis. The classical biochemical signature of AD includes total tau (T-tau), phosphorylated tau (P-tau), and the 42 amino acid peptide (Aβ42) of amyloid-β. Recent observations suggest that the use of CSF Aβ42:Aβ40 ratio rather than CSF Aβ42 alone could contribute to reduce inter-laboratory variation in Aβ values and increasing diagnostic performance of the CSF AD biomarkers in routine practice. However, research efforts aimed at enriching the CSF biomarker panel are ongoing. The CSF AD signature is also crucial for the design of clinical trials for AD, since it best guarantees AD pathology as the cause of cognitive impairment. Accordingly, CSF biomarkers have been now reported in the inclusion criteria of Phase I, Phase II, and Phase III clinical trials as enrichment strategy. So far, one of the most important reasons for the failure of AD clinical trials was the inclusion of participants with unlikely AD pathology. In order to implement the use of CSF biomarkers in AD routine diagnostic work-up and as accepted strategy for enriching trial populations, inter-laboratory variability should be minimized. Increasing efforts should also be devoted to promote data sharing practices, encouraging individual participant data meta-analyses.

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CitationGPTRetr445

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: data obtained from janelidze et al majbour olsson et al suárezcalvet and wellington et al Title of the paper: CSF markers for Alzheimer's disease: total tau, phospho-tau and Abeta42. Abstract of the paper: Today we have the first therapeutic compounds for treatment of Alzheimer's disease (AD) e.g. acetylcholine esterase inhibitors and in the near future we may expect new compounds such as gamma- and beta-secretase inhibitors. This has demanded increased accuracy in the diagnosis of AD and thus, among other possible approaches, diagnostic markers in the cerebrospinal fluid (CSF) have become a rapidly growing research field. Especially early in the course of the disease, when correct diagnosis is most difficult, such biomarkers would be especially valuable as one might expect the compounds to have the greatest potential of being effective. Two of the defining lesions in AD brains are senile plaques and neurofibrillary tangles with beta-amyloid (Abeta) and tau proteins as the main components respectively. Abeta and tau proteins are secreted to body fluids including plasma and cerebrospinal fluid (CSF). In this paper we review CSF markers for AD, with focus on their role in the clinical diagnosis. Reduced CSF levels of the 42 amino acid form of Abeta (Abeta42) and increased CSF levels of total tau (T-tau) in AD have been found in numerous studies, with high sensitivity figures. However, the specificity against other dementias is lower. The addition of phospho-tau (P-tau) seems to increase the specificity, since normal levels are found in other dementias and in cerebrovascular disease. An increasing number of studies suggests that these CSF markers perform well enough to have a role in the clinical work-up of patients with dementia if used together. We stress that the CSF markers should be combined with the clinical information and brain-imaging techniques.

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CitationGPTRetr446

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: data obtained from janelidze et al majbour olsson et al suárezcalvet and wellington et al Title of the paper: CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios: better diagnostic markers of Alzheimer disease. Abstract of the paper: OBJECTIVE The diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) must be improved before widespread clinical use. This study aimed to determine whether CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios are better diagnostic biomarkers of AD during both predementia and dementia stages in comparison to CSF Aβ42 alone. METHODS The study comprised three different cohorts (n = 1182) in whom CSF levels of Aβ42, Aβ40, and Aβ38 were assessed. CSF Aβs were quantified using three different immunoassays (Euroimmun, Meso Scale Discovery, Quanterix). As reference standard, we used either amyloid ((18)F-flutemetamol) positron emission tomography (PET) imaging (n = 215) or clinical diagnosis (n = 967) of well-characterized patients. RESULTS When using three different immunoassays in cases with subjective cognitive decline and mild cognitive impairment, the CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios were significantly better predictors of abnormal amyloid PET than CSF Aβ42. Lower Aβ42, Aβ42/Aβ40, and Aβ42/Aβ38 ratios, but not Aβ40 and Aβ38, correlated with smaller hippocampal volumes measured by magnetic resonance imaging. However, lower Aβ38, Aβ40, and Aβ42, but not the ratios, correlated with non-AD-specific subcortical changes, that is, larger lateral ventricles and white matter lesions. Further, the Aβ42/Aβ40 and Aβ42/Aβ38 ratios showed increased accuracy compared to Aβ42 when distinguishing AD from dementia with Lewy bodies or Parkinson's disease dementia and subcortical vascular dementia, where all Aβs (including Aβ42) were decreased. INTERPRETATION The CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios are significantly better than CSF Aβ42 to detect brain amyloid deposition in prodromal AD and to differentiate AD dementia from non-AD dementias. The ratios reflect AD-type pathology better, whereas decline in CSF Aβ42 is also associated with non-AD subcortical pathologies. These findings strongly suggest that the ratios rather than CSF Aβ42 should be used in the clinical work-up of AD.

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CitationGPTRetr447

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: data obtained from janelidze et al majbour olsson et al suárezcalvet and wellington et al Title of the paper: Moving fluid biomarkers for Alzheimer's disease from research tools to routine clinical diagnostics. Abstract of the paper: Four fluid-based biomarkers have been developed into diagnostic tests for Alzheimer's disease (AD) pathology: the ratio of 42 to 40 amino acid-long amyloid β, a marker of plaque pathology; total-tau and phosphorylated tau, markers of AD-related changes in tau metabolism and secretion; and neurofilament light, a marker of neurodegeneration. When measured in cerebrospinal fluid, these biomarkers can be used in clinical practice to support a diagnosis of mild cognitive impairment or dementia due to AD. Recently, technological breakthroughs have made it possible to measure them in standard blood samples as well. Here, we give an updated account of the current state of the fluid-based AD biomarker research field. We discuss how the new blood tests may be used in research and clinical practice, and what role they may play in relation to more established diagnostic tests, such as CSF biomarkers and amyloid and tau positron emission tomography, to facilitate the effective implementation of future disease-modifying therapies.

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CitationGPTRetr448

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: data obtained from janelidze et al majbour olsson et al suárezcalvet and wellington et al Title of the paper: Cerebrospinal Fluid Biomarkers of Alzheimer's Disease: Current Evidence and Future Perspectives. Abstract of the paper: Alzheimer's disease is a progressive, clinically heterogeneous, and particularly complex neurodegenerative disease characterized by a decline in cognition. Over the last two decades, there has been significant growth in the investigation of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease. This review presents current evidence from many clinical neurochemical studies, with findings that attest to the efficacy of existing core CSF biomarkers such as total tau, phosphorylated tau, and amyloid-β (Aβ42), which diagnose Alzheimer's disease in the early and dementia stages of the disorder. The heterogeneity of the pathophysiology of the late-onset disease warrants the growth of the Alzheimer's disease CSF biomarker toolbox; more biomarkers showing other aspects of the disease mechanism are needed. This review focuses on new biomarkers that track Alzheimer's disease pathology, such as those that assess neuronal injury (VILIP-1 and neurofilament light), neuroinflammation (sTREM2, YKL-40, osteopontin, GFAP, progranulin, and MCP-1), synaptic dysfunction (SNAP-25 and GAP-43), vascular dysregulation (hFABP), as well as CSF α-synuclein levels and TDP-43 pathology. Some of these biomarkers are promising candidates as they are specific and predict future rates of cognitive decline. Findings from the combinations of subclasses of new Alzheimer's disease biomarkers that improve their diagnostic efficacy in detecting associated pathological changes are also presented.

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CitationGPTRetr449

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: data obtained from janelidze et al majbour olsson et al suárezcalvet and wellington et al Title of the paper: Proteomic studies of cerebrospinal fluid biomarkers of Alzheimer's disease: an update. Abstract of the paper: Alzheimer's disease (AD) is a neurodegenerative disease affecting the brain. Today there are three cerebrospinal fluid (CSF) biomarkers, amyloid-β consisting of 42 amino acids (Aβ42), total-tau (t-tau) and phosphorylated-tau (p-tau), which combined have sensitivity and specificity figures around 80%. However, pathological studies have shown that comorbidity is a common feature in AD and that the three currently used CSF biomarkers do not optimally reflect the activity of the disease process. Thus, additional markers are needed. Areas covered: In the present review, we screened PubMed for articles published the last five years (2012-2017) for proteomic studies in CSF with the criteria that AD had to be included as one of the diagnostic groups. Based on inclusion criteria, 28 papers were included reporting in total 224 biomarker-data that were altered in AD compared to control. Both mass spectrometry and multi-panel immunoassays were considered as proteomic studies. Expert commentary: A large number of pilot studies have been reported but so far there is a lack of replicated findings and to date no CSF biomarker discovered in proteomic studies has reached the clinic to aid in the diagnostic work-up of patients with cognitive impairment.

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CitationGPTRetr450

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: data obtained from janelidze et al majbour olsson et al suárezcalvet and wellington et al Title of the paper: The clinical use of cerebrospinal fluid biomarker testing for Alzheimer's disease diagnosis: a consensus paper from the Alzheimer's Biomarkers Standardization Initiative. Abstract of the paper: BACKGROUND Cerebrospinal fluid (CSF) biomarkers β-amyloid 1-42 (Aβ1-42), also expressed as Aβ1-42:Aβ1-40 ratio, T-tau, and P-tau181P, have proven diagnostic accuracy for mild cognitive impairment and Alzheimer's disease (AD). How to use, interpret, and disclose biomarker results drives the need for standardization. METHODS Previous Alzheimer's Biomarkers Standardization Initiative meetings discussed preanalytical issues affecting Aβ1-42 and tau in CSF. This second round of consensus meetings focused on issues related to clinical use of AD CSF biomarkers. RESULTS Consensus was reached that lumbar puncture for AD CSF biomarker analysis be considered as a routine clinical test in patients with early-onset dementia, at the prodromal stage or with atypical AD. Moreover, consensus was reached on which biomarkers to use, how results should be interpreted, and potential confounding factors. CONCLUSIONS Changes in Aβ1-42, T-tau, and P-tau181P allow diagnosis of AD in its prodromal stage. Conversely, having all three biomarkers in the normal range rules out AD. Intermediate conditions require further patient follow-up.

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CitationGPTRetr451

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: data obtained from janelidze et al majbour olsson et al suárezcalvet and wellington et al Title of the paper: CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis. Abstract of the paper: BACKGROUND Alzheimer's disease biomarkers are important for early diagnosis in routine clinical practice and research. Three core CSF biomarkers for the diagnosis of Alzheimer's disease (Aβ42, T-tau, and P-tau) have been assessed in numerous studies, and several other Alzheimer's disease markers are emerging in the literature. However, there have been no comprehensive meta-analyses of their diagnostic performance. We systematically reviewed the literature for 15 biomarkers in both CSF and blood to assess which of these were most altered in Alzheimer's disease. METHODS In this systematic review and meta-analysis, we screened PubMed and Web of Science for articles published between July 1, 1984, and June 30, 2014, about CSF and blood biomarkers reflecting neurodegeneration (T-tau, NFL, NSE, VLP-1, and HFABP), APP metabolism (Aβ42, Aβ40, Aβ38, sAPPα, and sAPPβ), tangle pathology (P-tau), blood-brain-barrier function (albumin ratio), and glial activation (YKL-40, MCP-1, and GFAP). Data were taken from cross-sectional cohort studies as well as from baseline measurements in longitudinal studies with clinical follow-up. Articles were excluded if they did not contain a cohort with Alzheimer's disease and a control cohort, or a cohort with mild cognitive impairment due to Alzheimer's disease and a stable mild cognitive impairment cohort. Data were extracted by ten authors and checked by two for accuracy. For quality assessment, modified QUADAS criteria were used. Biomarker performance was rated by random-effects meta-analysis based on the ratio between biomarker concentration in patients with Alzheimer's disease and controls (fold change) or the ratio between biomarker concentration in those with mild cognitive impariment due to Alzheimer's disease and those with stable mild cognitive impairment who had a follow-up time of at least 2 years and no further cognitive decline. FINDINGS Of 4521 records identified from PubMed and 624 from Web of Science, 231 articles comprising 15 699 patients with Alzheimer's disease and 13 018 controls were included in this analysis. The core biomarkers differentiated Alzheimer's disease from controls with good performance: CSF T-tau (average ratio 2·54, 95% CI 2·44-2·64, p<0·0001), P-tau (1·88, 1·79-1·97, p<0·0001), and Aβ42 (0·56, 0·55-0·58, p<0·0001). Differentiation between cohorts with mild cognitive impairment due to Alzheimer's disease and those with stable mild cognitive impairment was also strong (average ratio 0·67 for CSF Aβ42, 1·72 for P-tau, and 1·76 for T-tau). Furthermore, CSF NFL (2·35, 1·90-2·91, p<0·0001) and plasma T-tau (1·95, 1·12-3·38, p=0·02) had large effect sizes when differentiating between controls and patients with Alzheimer's disease, whereas those of CSF NSE, VLP-1, HFABP, and YKL-40 were moderate (average ratios 1·28-1·47). Other assessed biomarkers had only marginal effect sizes or did not differentiate between control and patient samples. INTERPRETATION The core CSF biomarkers of neurodegeneration (T-tau, P-tau, and Aβ42), CSF NFL, and plasma T-tau were strongly associated with Alzheimer's disease and the core biomarkers were strongly associated with mild cognitive impairment due to Alzheimer's disease. Emerging CSF biomarkers NSE, VLP-1, HFABP, and YKL-40 were moderately associated with Alzheimer's disease, whereas plasma Aβ42 and Aβ40 were not. Due to their consistency, T-tau, P-tau, Aβ42, and NFL in CSF should be used in clinical practice and clinical research. FUNDING Swedish Research Council, Swedish State Support for Clinical Research, Alzheimer's Association, Knut and Alice Wallenberg Foundation, Torsten Söderberg Foundation, Alzheimer Foundation (Sweden), European Research Council, and Biomedical Research Forum.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: data obtained from janelidze et al majbour olsson et al suárezcalvet and wellington et al Title of the paper: CSF total tau, Abeta42 and phosphorylated tau protein as biomarkers for Alzheimer's disease. Abstract of the paper: With the arrival of effective symptomatic treatments and the promise of drugs that may delay progression, we now need to identify Alzheimer's disease (AD) at an early stage of the disease. To diagnose AD earlier and more accurately, attention has been directed toward peripheral biochemical markers. This article reviews promising potential cerebrospinal fluid (CSF) biomarkers for AD focussing on their role in clinical diagnosis. In particular, two biochemical markers, CSF total tau (t-tau) protein and the 42 amino acid form of beta-amyloid (Abeta42), perform satisfactorily enough to achieve a role in the clinical diagnostic settings of patients with dementia together with the cumulative information from basic clinical work-up, genetic screening, and brain imaging. These CSF markers are particularly useful to discriminate early or incipient AD from age-associated memory impairment, depression, and some secondary dementias. In order to discriminate AD from other primary dementia disorders, however, more accurate and specific markers are needed. Preliminary evidence strongly suggests that quantification of tau phosphorylated at specific sites in CSF improves early detection, differential diagnosis, and tracking of disease progression in AD.

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CitationGPTRetr453

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: data obtained from janelidze et al majbour olsson et al suárezcalvet and wellington et al Title of the paper: CSF Biomarkers of Alzheimer Disease in Patients With Concomitant α-Synuclein Pathology. Abstract of the paper: BACKGROUND AND OBJECTIVES Cerebrospinal fluid (CSF) biomarkers amyloid-β42 (Aβ42), phosphorylated tau (p-tau181), total tau (t-tau) and neurogranin (Ng) can diagnose Alzheimer's disease (AD) in life. However, it is unknown if CSF concentrations, and thus their accuracies, are affected by concomitant pathologies common in AD, such as α-synuclein (αSyn). Our primary goal was to test if biomarkers in patients with AD are altered by concomitant αSyn. We compared CSF Aβ42, p-tau181, t-tau and Ng levels across autopsy-confirmed AD and concomitant AD and αSyn (AD+αSyn). Antemortem CSF levels were related to postmortem accumulations of αSyn. Finally, we tested how concommitant AD+αSyn affected diagnostic accuracy of two CSF-based strategies: the ATN framework and the t-tau/Aβ42 ratio. METHODS Inclusion criteria were neuropathologic diagnoses of AD, mixed AD+αSyn, and αSyn. A convenience sample of non-impaired controls were selected with available CSF and a mini mental state exam (MMSE)≥27. αSyn without AD and controls were included as reference groups. Analyses of covariance (ANCOVAs) tested planned comparisons were CSF Aβ42, p-tau181, t-tau, and Ng differences across AD and AD+αSyn. Linear models tested how biomarkers were altered by αSyn accumulation in AD, accounting for pathologic amyloid-β and tau. Receiver operating characteristic and area under the curve (AUC), including 95% confidence intervals (CI), evaluated diagnostic accuracy. RESULTS Participants were 61 AD, 39 mixed AD+αSyn, 20 αSyn, and 61 Controls. AD had similar median age (73 [IQR=12]), MMSE (23 [IQR=9]), and sex distribution (Male=49%) compared to AD+αSyn age (70 [IQR=13]; p=0.3), MMSE (25 [IQR=9.5]; p=0.19), and sex distribution (Male=69%; p=0.077). ANCOVAs showed AD+αSyn had lower p-tau181 (F(1,94)=17, p=0), t-tau (F(1,93)=11, p=0.0004), and Ng levels (F(1,50)=12, p=0.0004) than AD; there was no difference in Aβ42 (p=0.44). Models showed increasing αSyn related to lower p-tau181 (β=-0.26, SE=0.092, p=0.0065), t-tau (β=-0.19, SE=0.092, p=0.041), and Ng levels (β=-0.2, SE=0.066, p=0.0046); αSyn was not a significant factor for Aβ42 (p=1). T-tau/Aβ42 had the highest accuracy when detecting AD, including mixed AD+αSyn cases (AUC=0.95; CI=0.92 to 0.98). DISCUSSION Findings demonstrate that concomitant αSyn pathology in AD is associated with lower CSF p-tau181, t-tau, and Ng levels, and can affect diagnositic accuracy in AD patients.

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CitationGPTRetr454

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: data obtained from janelidze et al majbour olsson et al suárezcalvet and wellington et al Title of the paper: Cerebrospinal fluid biomarkers for disease stage and intensity in cognitively impaired patients. Abstract of the paper: Biomarkers to monitor the degenerative process in Alzheimer's disease would be of great value. We examined the relation between cerebrospinal fluid (CSF) total tau (T-tau), phospho-tau (P-tau) and Abeta42 and magnetic resonance imaging (MRI) measures of brain atrophy. CSF was taken at baseline and MRI at baseline and at 16 months follow-up. At baseline, statistically significantly lower Abeta42 were found with lower brain volume (r=0.55; P<0.0001) and larger ventricular volume (r=-0.53; P<0.001). In contrast, statistically significantly higher T-tau (r=0.47; P<0.001) and P-tau (r=0.41; P=0.005) were found with more marked ventricular widening during the follow-up period. These results suggest that Abeta42 in CSF reflects the stage of the disease, with lower CSF levels as the disease progresses, while T-tau and P-tau reflect the intensity of the disease process, with higher CSF-levels with a more rapid progression.

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CitationGPTRetr455

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: data obtained from janelidze et al majbour olsson et al suárezcalvet and wellington et al Title of the paper: Measurement of thirteen biological markers in CSF of patients with Alzheimer's disease and other dementias. Abstract of the paper: Cerebrospinal fluid (CSF) biological markers may be of valuable help in the diagnosis of dementia. The aim of the present study was to evaluate CSF levels of 13 potential biomarkers in patients with Alzheimer's disease (AD), frontotemporal lobe dementia, alcohol dementia, major depression and control patients without any neuropsychiatric disease. The study was performed using beta-amyloid 1-42 (Abeta42), total tau and phosphorylated tau-181 (P-tau181) as core markers. The ratio P-tau181/Abeta42 could significantly distinguish AD patients from all other diagnostic subgroups. CSF levels of 5 growth factors (HGF, GDNF, VEGF, BDNF, FGF-2) and 3 cytokines/chemokines (TNF-alpha, TGF-beta1, MIP-1alpha) did not significantly differentiate between the studied groups. However, depending on the degree of neurodegeneration (as expressed by the ratio P-tau181/Abeta42), patients with AD displayed significantly increased CSF levels of nerve growth factor (NGF) as compared to healthy controls. CSF levels of monocyte chemoattractant protein 1 (MCP-1) were found to be significantly increased with age in all groups but did not distinguish AD patients from healthy controls. The results confirmed the suitability of the ratio P-tau181/Abeta42 for the diagnosis of AD, while CSF levels of NGF and MCP-1 are less specific and reliable for AD. It is suggested that the increase in NGF depends on the extent of neurodegeneration of the AD type and the increase in MCP-1 on age.

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CitationGPTRetr456

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: data obtained from janelidze et al majbour olsson et al suárezcalvet and wellington et al Title of the paper: Cerebrospinal Fluid Biomarkers for Target Engagement and Efficacy in Clinical Trials for Alzheimer's and Parkinson's Diseases. Abstract of the paper: BACKGROUND Cerebrospinal fluid (CSF) is increasingly being used to detect biochemical changes that occur in different neurological conditions. In Alzheimer's disease (AD), three CSF biomarkers (Aβ42, total tau, and phosphorylated tau) are used in clinical practice to support the diagnosis in the prodromal stages of the disease. In Parkinson's disease (PD), the investigation is following the pathway of AD research and some promising markers have been identified, with the main aim to favor an early diagnosis, i.e. in the premotor phase. Some of these CSF markers have also been incorporated in AD and PD clinical trials to demonstrate target engagement of the drug and/or to enrich the patient populations. In this chapter, we will review the main CSF biomarkers for AD and PD and their potential application to clinical trials. SUMMARY In clinical trials assessing the efficacy of disease-modifying agents for AD, CSF biomarkers are currently used both as a diagnostic criterion for inclusion and for monitoring the biochemical impact of the drug on the upstream neurodegenerative mechanisms. Accordingly, recent trials devoted to PD are following such a procedure, although in this neurodegenerative disorder CSF biomarkers are not ready yet for routine clinical use. KEY MESSAGES AD and PD are neurodegenerative disorders that share a long asymptomatic/prodromal phase in which neurodegenerative phenomena already take place in the brain. Clinical trials assessing the efficacy of disease-modifying agents should include the CSF measurement of related biomarkers as biochemical proof of the underlying pathology as well as of the impact of the drug on these pathogenic mechanisms.

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CitationGPTRetr457

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: data obtained from janelidze et al majbour olsson et al suárezcalvet and wellington et al Title of the paper: Cerebrospinal fluid tau, A beta, and phosphorylated tau protein for the diagnosis of Alzheimer's disease. Abstract of the paper: The diagnosis of AD is still largely based on exclusion criteria of secondary causes and other forms of dementia with similar clinical pictures, than the diagnostic accuracy of AD is low. Improved methods of early diagnosis are needed, particularly because drugs treatment is more effective in the early stages of the disease. Recent research focused the attention to biochemical diagnostic markers (biomarkers) and according to the proposal of a consensus group on biomarkers, three candidate CSF markers reflecting the pathological AD processes, have recently been identified: total tau protein (t-tau), amyloid beta(1-42) protein (A beta42), and tau protein phosphorylated at AD-specific epitopes (p-tau). Several articles report reduced CSF levels of A beta42 and increased CSF levels of t-tau and p-tau in AD; the sensitivity and specificity of these data are able for discrimination of AD patients from controls. However, the specificity for other dementias is low. According to the literature analysis reported in the present review, we can conclude that the combination of the CSF markers and their ratios may significantly increase the specificity and the accuracy of AD diagnosis.

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CitationGPTRetr458

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: data obtained from janelidze et al majbour olsson et al suárezcalvet and wellington et al Title of the paper: Cerebrospinal fluid tau and beta-amyloid in Alzheimer patients, disease controls and an age-matched random sample. Abstract of the paper: We prospectively evaluated the diagnostic accuracy of cerebrospinal fluid (CSF)-beta-amyloid1-42 (Abeta42), -total-tau (tau) and -phosphorylated-tau181 (p-tau181) as measured by sandwich ELISAs in the clinical routine of a community state hospital to discriminate between patients with Alzheimer's disease (AD), healthy controls (HC), non-AD-dementias, a group composed of various psychiatric disorders (non-AD-dementias, mental diseases) and an age-matched random sample (RS) (total N=219). By comparing patients with AD to HC as reference, tau revealed sensitivity (sens)/specificity (spec) of 88%/80%, p-tau(181) 88%/80%, tau/Abeta42-ratio 81%/85% and phospho-tau(181)/Abeta42-ratio 81%/78%. Discriminative power between HC and all dementias under investigation was estimated lower for tau (78%/77%) and p-tau(181) (73%/79%). Relative to patients with AD, ROC analysis for the RS revealed highest sens/spec for p-tau181 (79%/77%) and p-tau181/Abeta42 ratio (78%/75%). Differentiation between AD versus a group made of patients with various psychiatric disorders was optimised by using CSF-p-tau181 (80%/77%). Under clinical routine conditions current CSF-biomarkers show a substantial capacity to discriminate between AD and HC as reference and to mark off AD patients from RS and heterogeneous diagnostic groups composed of non-AD dementias and other psychiatric conditions. Despite a residual substantial overlap between the groups, we conclude that current CSF markers are well suited to support AD-related diagnostic procedures in every-day clinics.

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CitationGPTRetr459

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: data obtained from janelidze et al majbour olsson et al suárezcalvet and wellington et al Title of the paper: Clinical application of CSF biomarkers for Alzheimer's disease: From rationale to ratios. Abstract of the paper: Biomarker testing is recommended for the accurate and timely diagnosis of Alzheimer's disease (AD). Using illustrative case narratives we consider how cerebrospinal fluid (CSF) biomarker tests may be used in different presentations of cognitive impairment to facilitate timely and differential diagnosis, improving diagnostic accuracy, providing prognostic information, and guiding personalized management in diverse scenarios. Evidence shows that (1) CSF ratios are superior to amyloid beta (Aβ)1-42 alone; (2) concordance of CSF ratios to amyloid positron emission tomography (PET) is better than Aβ1-42 alone; and (3) phosphorylated tau (p-tau)/Aβ1-42 ratio is superior to p-tau alone. CSF biomarkers are recommended for the exclusion of AD as the underlying cause of cognitive impairment, diagnosis of AD at an early stage, differential diagnosis of AD in individuals presenting with other neuropsychiatric symptoms, accurate diagnosis of AD in an atypical presentation, and for clinical trial enrichment. Highlights Cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarker testing may be underused outside specialist centers.CSF biomarkers improve diagnostic accuracy, guiding personalized management of AD.CSF ratios (amyloid beta [Aβ]1-42/Aβ1-40 and phosphorylated tau/Aβ1-42) perform better than single markers.CSF ratios produce fewer false-negative and false-positive results than individual markers.CSF biomarkers should be included in diagnostic work-up of AD and mild cognitive impairment due to AD.

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CitationGPTRetr460

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intriguingly on one hand in many ad models and patients increasing data indicated that the genetic and nongenetic risk factors for ad could lead to brain cholesterol deficiency which means a direct causative link between brain cholesterol loss and ad fad and sad Title of the paper: Cholesterol in Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is the most common form of neurodegenerative dementia and affects up to 15 million people worldwide. Although no single cause of AD has been identified, recent research has suggested that several pathogenetic factors influence risk and expression. A growing amount of evidence underscores a mechanistic link between cholesterol metabolism in the brain and the formation of amyloid plaques. Excess brain cholesterol has been associated with increased formation and deposition of amyloid-beta peptide from amyloid precursor protein. Cholesterol-lowering statins have become a focus of research in AD. Genetic polymorphisms associated with pivotal points in cholesterol metabolism in brain tissues may contribute to the risk and pathogenesis of AD. In this review, we summarise current knowledge of the role of cholesterol metabolism in the pathogenesis of AD and examine the potential of statins in the prevention and treatment of AD.

False

CitationGPTRetr461

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intriguingly on one hand in many ad models and patients increasing data indicated that the genetic and nongenetic risk factors for ad could lead to brain cholesterol deficiency which means a direct causative link between brain cholesterol loss and ad fad and sad Title of the paper: Alzheimer's disease and cholesterol: the fat connection. Abstract of the paper: Since the discovery of the significance of the cholesterol-carrying apolipoprotein E and cholesterolaemia as major risk factors for Alzheimer's Disease (AD) there has been a mounting interest in the role of this lipid as a possible pathogenic agent. In this review we analyse the current evidence linking cholesterol metabolism and regulation in the CNS with the known mechanisms underlying the development of Alzheimer's Disease. Cholesterol is known to affect amyloid-beta generation and toxicity, although it must be considered that the results studies using the statin class of drugs to lower plasma cholesterol may be affected by other effects associated with these drugs. Finally, we report some of our results pointing at the interplay between neurons and astrocytes and NADPH oxidase activation as a new candidate mechanism linking cholesterol and AD pathology.

False

CitationGPTRetr462

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intriguingly on one hand in many ad models and patients increasing data indicated that the genetic and nongenetic risk factors for ad could lead to brain cholesterol deficiency which means a direct causative link between brain cholesterol loss and ad fad and sad Title of the paper: Imbalanced cholesterol metabolism in Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative disease that is mainly caused by β-amyloid accumulation. A large number of studies have shown that elevated cholesterol levels may perform a function in AD pathology, and several cholesterol-related gene polymorphisms are associated with this disease. Although numerous studies have shown the important function of cholesterol in AD pathogenesis and development, the underlying mechanism remains unclear. To further elucidate cholesterol metabolism disorder and AD, we first, review metabolism and regulation of the cholesterol in the brain. Second, we summarize the literature stating that hypercholesterolemia is one of the risk factors of AD. Third, we discuss the main mechanisms of abnormal cholesterol metabolism that increase the risk of AD. Finally, the relationships between AD and apolipoprotein E, PCSK9, and LRP1 are discussed in this article.

False

CitationGPTRetr463

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intriguingly on one hand in many ad models and patients increasing data indicated that the genetic and nongenetic risk factors for ad could lead to brain cholesterol deficiency which means a direct causative link between brain cholesterol loss and ad fad and sad Title of the paper: Cholesterol at the crossroads: Alzheimer's disease and lipid metabolism. Abstract of the paper: Alzheimer's Disease (AD) is a devastating disease that affects millions of elderly persons. Despite years of intense investigations, genetic risk factors that affect the majority of AD cases have yet to be determined. Recent studies suggest that cholesterol metabolism has integral part in AD pathogenesis, suggesting that genes that regulate lipid metabolism may also play roles in AD. This review will first describe emerging evidence that links cholesterol to the mechanisms thought to underlie AD. Based on this rationale, candidate genes located in regions implicated in AD that have roles in lipid metabolism will then be discussed.

False

CitationGPTRetr464

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intriguingly on one hand in many ad models and patients increasing data indicated that the genetic and nongenetic risk factors for ad could lead to brain cholesterol deficiency which means a direct causative link between brain cholesterol loss and ad fad and sad Title of the paper: Alzheimer's disease: the cholesterol connection. Abstract of the paper: A hallmark of all forms of Alzheimer's disease (AD) is an abnormal accumulation of the beta-amyloid protein (Abeta) in specific brain regions. Both the generation and clearance of Abeta are regulated by cholesterol. Elevated cholesterol levels increase Abeta in cellular and most animals models of AD, and drugs that inhibit cholesterol synthesis lower Abeta in these models. Recent studies show that not only the total amount, but also the distribution of cholesterol within neurons, impacts Abeta biogenesis. The identification of a variant of the apolipoprotein E (APOE) gene as a major genetic risk factor for AD is also consistent with a role for cholesterol in the pathogenesis of AD. Clinical trials have recently been initiated to test whether lowering plasma and/or neuronal cholesterol levels is a viable strategy for treating and preventing AD. In this review, we describe recent findings concerning the molecular mechanisms underlying the cholesterol-AD connection.

False

CitationGPTRetr465

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intriguingly on one hand in many ad models and patients increasing data indicated that the genetic and nongenetic risk factors for ad could lead to brain cholesterol deficiency which means a direct causative link between brain cholesterol loss and ad fad and sad Title of the paper: Plasma cholesterol and risk for late-onset Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD), the most common cause of dementia, is a progressive neurodegenerative disorder affecting millions of people worldwide. AD has a multifactorial origin, resulting from an interaction between genetic susceptibility and environmental risk factors. Genetic, epidemiological, experimental and clinical data strongly suggest that the metabolism of cholesterol has an important role in AD pathogenesis. Several studies have demonstrated that high concentrations of serum cholesterol increase the risk of AD. Statins, drugs that reduce cholesterol levels, have been investigated as a possible treatment for AD. However, the literature is not exempt of contradictory results. In this article, we review a recent article by Reitz et al. demonstrating that higher levels of high-density lipoprotein cholesterol, total cholesterol and non-high-density lipoprotein cholesterol are associated with lower risk of AD. In addition, we discuss the current state of knowledge regarding the relationship between plasma cholesterol and AD, stressing the need for understanding the molecular mechanisms behind this association.

False

CitationGPTRetr466

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intriguingly on one hand in many ad models and patients increasing data indicated that the genetic and nongenetic risk factors for ad could lead to brain cholesterol deficiency which means a direct causative link between brain cholesterol loss and ad fad and sad Title of the paper: Alzheimer's disease: cholesterol a menace? Abstract of the paper: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease manifested by cognitive and memory deterioration, culminating in a spectrum of neuropsychiatric disturbances and the impairment of daily activities. AD is a multifactorial disease with a range of contributing factors which includes genes and diet. The magnitude of AD is reflected in the loss of individuality of the affected person and in the terminal course through which the disease develops. In this review, we aim to provide a background on AD and the contribution of cholesterol in the etiology of Alzheimer's. Cholesterol seems to be intimately linked with the generation of amyloid plaques, which is central to the pathogenesis of AD. Although there are conflicting reports on the role of cholesterol in AD, majority of the studies point out the positive association of cholesterol with AD.

False

CitationGPTRetr467

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intriguingly on one hand in many ad models and patients increasing data indicated that the genetic and nongenetic risk factors for ad could lead to brain cholesterol deficiency which means a direct causative link between brain cholesterol loss and ad fad and sad Title of the paper: The link between cholesterol and Alzheimer's disease. Abstract of the paper: A leading hypothesis on the pathophysiology of Alzheimer's disease (AD) is the mis-metabolism of amyloid precursor protein. This mis-metabolism causes the 42-amino acid form of A beta(Abeta42) to form oligomers that in turn start a chain of events leading to the accumulation of amyloid plaques. Vascular factors such as hypertension, hypercholesterolemia and diabetes as well as the inheritance of the epsilon4 allele of the ApoE gene are risk factors for AD. These risks are thought to promote the production of beta-amyloid (Abeta). An association between cholesterol and the development of AD was suggested in 1994 and since then, research has confirmed a link between cholesterol and the development of AD. A high cholesterol level in mid-life is a risk for AD and statins i.e. cholesterol-lowering drugs, reduce this risk. Statins inhibit enzymes involved in the endogenous synthesis of cholesterol and evidence is mounting that they also affect enzymes in Abeta metabolism i.e. beta-secretase. This normalises the breakdown of the precursor of Abeta, amyloid precursor protein, thereby promoting the nonamyloidogenic pathway. This review focusses on the link between cholesterol and Alzheimer's disease.

False

CitationGPTRetr468

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intriguingly on one hand in many ad models and patients increasing data indicated that the genetic and nongenetic risk factors for ad could lead to brain cholesterol deficiency which means a direct causative link between brain cholesterol loss and ad fad and sad Title of the paper: Cholesterol and Alzheimer's Disease; From Risk Genes to Pathological Effects. Abstract of the paper: While the central nervous system compromises 2% of our body weight, it harbors up to 25% of the body's cholesterol. Cholesterol levels in the brain are tightly regulated for physiological brain function, but mounting evidence indicates that excessive cholesterol accumulates in Alzheimer's disease (AD), where it may drive AD-associated pathological changes. This seems especially relevant for late-onset AD, as several of the major genetic risk factors are functionally associated with cholesterol metabolism. In this review we discuss the different systems that maintain brain cholesterol metabolism in the healthy brain, and how dysregulation of these processes can lead, or contribute to, Alzheimer's disease. We will also discuss how AD-risk genes might impact cholesterol metabolism and downstream AD pathology. Finally, we will address the major outstanding questions in the field and how recent technical advances in CRISPR/Cas9-gene editing and induced pluripotent stem cell (iPSC)-technology can aid to study these problems.

False

CitationGPTRetr469

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intriguingly on one hand in many ad models and patients increasing data indicated that the genetic and nongenetic risk factors for ad could lead to brain cholesterol deficiency which means a direct causative link between brain cholesterol loss and ad fad and sad Title of the paper: The link between altered cholesterol metabolism and Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD), the most common form of dementia, is characterized by the progressive loss of neurons and synapses, and by extracellular deposits of amyloid-β (Aβ) as senile plaques, Aβ deposits in the cerebral blood vessels, and intracellular inclusions of hyperphosphorylated tau in the form of neurofibrillary tangles. Several mechanisms contribute to AD development and progression, and increasing epidemiological and molecular evidence suggests a key role of cholesterol in its initiation and progression. Altered cholesterol metabolism and hypercholesterolemia appear to play fundamental roles in amyloid plaque formation and tau hyperphosphorylation. Over the last decade, growing evidence supports the idea that cholesterol oxidation products, known as oxysterols, may be the missing link between altered brain cholesterol metabolism and AD pathogenesis, as their involvement in neurotoxicity, mainly by interacting with Aβ peptides, is reported.

False

CitationGPTRetr470

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intriguingly on one hand in many ad models and patients increasing data indicated that the genetic and nongenetic risk factors for ad could lead to brain cholesterol deficiency which means a direct causative link between brain cholesterol loss and ad fad and sad Title of the paper: Oxysterols and Alzheimer's disease. Abstract of the paper: There is a clear link between cholesterol turnover and neurodegenerative diseases and hypercholesterolemia is an established risk factor for Alzheimer's disease (AD). The failure to demonstrate a transfer of cholesterol from the circulation into the brain in humans and experimental animals makes it difficult to explain the link between hypercholesterolemia and AD. In contrast to cholesterol itself, side-chain oxidized cholesterol metabolites such as 24S-hydroxycholesterol and 27-hydroxycholesterol are able to pass the blood-brain barrier (BBB). Formation of 24S-hydroxycholesterol is the quantitatively most important mechanism for elimination of cholesterol from the brain and we recently demonstrated a significant net uptake of 27-hydroxycholesterol by the brain from the circulation. We have also shown that patients with AD have increased brain levels of 27-hydroxycholesterol, which may affect the production of beta-amyloid in the brain. The levels of 27-hydroxycholesterol in the circulation are correlated with the levels of cholesterol and the possibility must be considered that the flux of 27-hydroxycholesterol into the brain is the missing link between hypercholesterolemia and Alzheimer's disease. Current knowledge about the role of the two oxysterols for cholesterol homeostasis in the brain as well as their diagnostic potential are reviewed.

False

CitationGPTRetr471

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intriguingly on one hand in many ad models and patients increasing data indicated that the genetic and nongenetic risk factors for ad could lead to brain cholesterol deficiency which means a direct causative link between brain cholesterol loss and ad fad and sad Title of the paper: Regulation of cerebral cholesterol metabolism in Alzheimer disease. Abstract of the paper: Alzheimer disease (AD) is an age-related neurodegenerative disorder that manifests as a progressive loss of memory and deterioration of higher cognitive functions. Alzheimer disease is characterized by accumulation in the brain of the β-amyloid peptide generated by β- and γ-secretase processing of amyloid precursor protein. Epidemiological studies have linked elevated plasma cholesterol and lipoprotein levels in midlife with AD development. Cholesterol-fed animal models exhibit neuropathologic features of AD including accumulation of β-amyloid peptide. Specific isoforms of the cholesterol transporter apolipoprotein E are associated with susceptibility to AD. Although multiple lines of evidence indicate a role for cholesterol in AD, the exact impact and mechanisms involved remain largely unknown. This review summarizes the current state of our knowledge of the influence of cholesterol and lipid pathways in AD pathogenesis in vitro and in vivo.

False

CitationGPTRetr472

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intriguingly on one hand in many ad models and patients increasing data indicated that the genetic and nongenetic risk factors for ad could lead to brain cholesterol deficiency which means a direct causative link between brain cholesterol loss and ad fad and sad Title of the paper: Neuronal cholesterol esterification by ACAT1 in Alzheimer's disease. Abstract of the paper: Cholesterol has been implicated in various neurodegenerative diseases. Here we review the connection between cholesterol and Alzheimer's disease (AD), focusing on a recent study that links neuronal cholesterol esterification with biosynthesis of 24(S)-hydroxycholesterol and the fate of human amyloid precursor protein in a mouse model of AD. We also briefly evaluate the potential of ACAT1 as a drug target for AD.

False

CitationGPTRetr473

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intriguingly on one hand in many ad models and patients increasing data indicated that the genetic and nongenetic risk factors for ad could lead to brain cholesterol deficiency which means a direct causative link between brain cholesterol loss and ad fad and sad Title of the paper: Novel therapeutic strategies for Alzheimer's disease targeting brain cholesterol homeostasis. Abstract of the paper: Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. Aβ plaques and tauopathy are two major concerns associated with AD. Moreover, excessive Aβ accumulation can lead to other nonspecific metabolic brain abnormalities. There are various genetic, environmental, and other risk factors associated with AD. Identification of risk factors and its mechanisms by which these factors impart role in AD pathology would be helpful for the prevention of AD progression. Altered cholesterol homeostasis could be considered as a risk factor for AD progression. Brain cholesterol dysmetabolism is recognized as one of the crucial attributes for AD that affect major hallmarks of AD including neurodegeneration. To fill the gap between altered cholesterol levels in the brain and AD, the researchers started focusing on statins as re-purposing drugs for AD treatment. The various other hypothesis has been suggested due to a lack of beneficial results of statins in clinical trials, such as reduced brain cholesterol could underlie poor cognition. Unfortunately, it is still unclear, whether an increase or decrease in brain cholesterol levels responsible for Alzheimer's disease or not. Presently, scientists believed that managing the level of cholesterol in the brain may help as an alternative treatment strategy for AD. In this review, we focused on the therapeutic strategies for AD by targeting brain cholesterol levels.

False

CitationGPTRetr474

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intriguingly on one hand in many ad models and patients increasing data indicated that the genetic and nongenetic risk factors for ad could lead to brain cholesterol deficiency which means a direct causative link between brain cholesterol loss and ad fad and sad Title of the paper: Cholesterol and Alzheimer's disease--is there a relation? Abstract of the paper: The predominating theory on the pathophysiology of Alzheimer's disease (AD) concerns the mis-metabolism of amyloid precursor protein (APP). As a result of this mis-metabolism, there is an increased production of the 42 amino acid form of beta-amyloid (Abeta42) that rapidly will form oligomers that initiates a cascade of events leading to the accumulation of amyloid plaques. Commonly recognised as vascular factors, hypertension, hypercholesterolemia and diabetes and the inheritance of the epsilon4 allele of the APOE gene, are also risk factors for AD. These risks have been found to promote the production of Abeta42. An association between cholesterol and the development of AD was suggested in the early 1990s and ever since, an increasing amount of research has confirmed that there is a link between cholesterol and the development of AD. A high cholesterol levels in mid-life is a risk for AD and statins, i.e., cholesterol-lowering drugs, reduce this risk. Statins may not only inhibit enzymes involved in the endogenous synthesis of cholesterol but also affect enzymes involved in Abeta metabolism, i.e., alpha-secretase and beta-secretase. This normalises the breakdown of APP thereby promoting the non-amyloidogenic pathway. In this review, investigations focusing on cholesterol and Alzheimer's disease are presented.

False

CitationGPTRetr475

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intriguingly on one hand in many ad models and patients increasing data indicated that the genetic and nongenetic risk factors for ad could lead to brain cholesterol deficiency which means a direct causative link between brain cholesterol loss and ad fad and sad Title of the paper: Cholesterol in brain disease: sometimes determinant and frequently implicated. Abstract of the paper: Cholesterol is essential for neuronal physiology, both during development and in the adult life: as a major component of cell membranes and precursor of steroid hormones, it contributes to the regulation of ion permeability, cell shape, cell-cell interaction, and transmembrane signaling. Consistently, hereditary diseases with mutations in cholesterol-related genes result in impaired brain function during early life. In addition, defects in brain cholesterol metabolism may contribute to neurological syndromes, such as Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD), and even to the cognitive deficits typical of the old age. In these cases, brain cholesterol defects may be secondary to disease-causing elements and contribute to the functional deficits by altering synaptic functions. In the first part of this review, we will describe hereditary and non-hereditary causes of cholesterol dyshomeostasis and the relationship to brain diseases. In the second part, we will focus on the mechanisms by which perturbation of cholesterol metabolism can affect synaptic function.

True

CitationGPTRetr476

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intriguingly on one hand in many ad models and patients increasing data indicated that the genetic and nongenetic risk factors for ad could lead to brain cholesterol deficiency which means a direct causative link between brain cholesterol loss and ad fad and sad Title of the paper: Cholesterol, lipids, amyloid Beta, and Alzheimer's. Abstract of the paper: High levels of cholesterol have been proposed as a risk factor for Alzheimer's disease (AD). Polymorphism of genes encoding proteins that regulate cholesterol metabolism have also been associated with the frequency of Alzheimer's development. Some studies have shown that cholesterol-lowering drugs reduce the frequency of AD development. The proposed role of cholesterol in AD has been challenged by several studies. In this review, we provide a brief account of the major pieces of evidence in support of and against the possible role of cholesterol in the development of AD, and the methodologies used. We highlight the interactions between cholesterol and amyloid beta (Abeta) and, with the peptide's precursor protein. Drawing from our teams' recent findings, we speculate on how Abeta peptides may influence the fluidity, stability of the membrane, as well as membrane morphological changes.

False

CitationGPTRetr477

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intriguingly on one hand in many ad models and patients increasing data indicated that the genetic and nongenetic risk factors for ad could lead to brain cholesterol deficiency which means a direct causative link between brain cholesterol loss and ad fad and sad Title of the paper: Linking lipids to Alzheimer's disease: cholesterol and beyond. Abstract of the paper: Lipid-mediated signalling regulates a plethora of physiological processes, including crucial aspects of brain function. In addition, dysregulation of lipid pathways has been implicated in a growing number of neurodegenerative disorders, such as Alzheimer's disease (AD). Although much attention has been given to the link between cholesterol and AD pathogenesis, growing evidence suggests that other lipids, such as phosphoinositides and phosphatidic acid, have an important role. Regulators of lipid metabolism (for example, statins) are a highly successful class of marketed drugs, and exploration of lipid dysregulation in AD and identification of novel therapeutic agents acting through relevant lipid pathways offers new and effective options for the treatment of this devastating disorder.

False

CitationGPTRetr478

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intriguingly on one hand in many ad models and patients increasing data indicated that the genetic and nongenetic risk factors for ad could lead to brain cholesterol deficiency which means a direct causative link between brain cholesterol loss and ad fad and sad Title of the paper: Cholesterol in Alzheimer's disease and tauopathy. Abstract of the paper: Cholesterol has been implicated in the pathogenesis of amyloid plaques in Alzheimer's disease (AD) and in the formation of neurofibrillary pathology in Niemann-Pick disease. Several epidemiology studies have implicated high cholesterol as a risk factor for AD and have shown that the use of cholesterol-reducing agents (statins) can be protective against the disease. We and others have shown that cholesterol levels modulate the processing of the amyloid precursor protein (APP) both in vivo and in vitro, affecting the accumulation of A-beta (Abeta) peptides that may directly impact the risk of AD. Mutations in the Niemann-Pick C gene (NPC) result in deficient cholesterol transport/storage. Clinically, Niemann-Pick disease causes a severe childhood lipidosis, with neurodegeneration characterized by the presence of AD-type neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau. Studies of mouse models of NPC show that defects in cellular cholesterol trafficking are associated with enhanced generation of Abeta and the hyperphosphorylation of tau, further implicating the cholesterol homeostasis pathway as a risk factor for amyloidosis.

False

CitationGPTRetr479

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intriguingly on one hand in many ad models and patients increasing data indicated that the genetic and nongenetic risk factors for ad could lead to brain cholesterol deficiency which means a direct causative link between brain cholesterol loss and ad fad and sad Title of the paper: Alzheimer's disease--a dysfunction in cholesterol and lipid metabolism. Abstract of the paper: 1. Strong etiological association exists between dysfunctional metabolism of brain lipids, age-related changes in the cerebral vasculature and neurodegenerative features characteristic of Alzheimer's disease (AD) brain. 2. In this short review, recent experimental evidence for these associations is further discussed below.

False

CitationGPTRetr480

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aged companion animals exhibit brain pathologies that mirror those found in humans including plaques tangles vascular cerebral amyloid angiopathy caa myelin disruption lipofuscin neuronal vacuoles axonal degeneration and abnormalities in cholinergic neurons Title of the paper: Pathology of the Aging Brain in Domestic and Laboratory Animals, and Animal Models of Human Neurodegenerative Diseases. Abstract of the paper: According to the WHO, the proportion of people over 60 years is increasing and expected to reach 22% of total world's population in 2050. In parallel, recent animal demographic studies have shown that the life expectancy of pet dogs and cats is increasing. Brain aging is associated not only with molecular and morphological changes but also leads to different degrees of behavioral and cognitive dysfunction. Common age-related brain lesions in humans include brain atrophy, neuronal loss, amyloid plaques, cerebrovascular amyloid angiopathy, vascular mineralization, neurofibrillary tangles, meningeal osseous metaplasia, and accumulation of lipofuscin. In aging humans, the most common neurodegenerative disorder is Alzheimer's disease (AD), which progressively impairs cognition, behavior, and quality of life. Pathologic changes comparable to the lesions of AD are described in several other animal species, although their clinical significance and effect on cognitive function are poorly documented. This review describes the commonly reported age-associated neurologic lesions in domestic and laboratory animals and the relationship of these lesions to cognitive dysfunction. Also described are the comparative interspecies similarities and differences to AD and other human neurodegenerative diseases including Parkinson's disease and progressive supranuclear palsy, and the spontaneous and transgenic animal models of these diseases.

True

CitationGPTRetr481

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aged companion animals exhibit brain pathologies that mirror those found in humans including plaques tangles vascular cerebral amyloid angiopathy caa myelin disruption lipofuscin neuronal vacuoles axonal degeneration and abnormalities in cholinergic neurons Title of the paper: Aging in the canine and feline brain. Abstract of the paper: Aging dogs and cats show neurodegenerative features that are similar to human aging and Alzheimer disease. Neuropathologic changes with age may be linked to signs of cognitive dysfunction both in the laboratory and in a clinic setting. Less is known about cat brain aging and cognition and this represents an area for further study. Neurodegenerative diseases such as lysosomal storage diseases in dogs and cats also show similar features of human aging, suggesting some common underlying pathogenic mechanisms and also suggesting pathways that can be modified to promote healthy brain aging.

False

CitationGPTRetr482

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aged companion animals exhibit brain pathologies that mirror those found in humans including plaques tangles vascular cerebral amyloid angiopathy caa myelin disruption lipofuscin neuronal vacuoles axonal degeneration and abnormalities in cholinergic neurons Title of the paper: Brain aging in dogs: parallels with human brain aging and Alzheimer's disease. Abstract of the paper: Differentiating normal from pathologic aging is a challenge to veterinarians treating geriatric patients and to clinicians diagnosing Alzheimer's disease. Part of the difficulty stems from the lack of a biological marker. Dogs and humans develop similar cognitive dysfunction with age, and a subset of individuals develop severe impairments. Similar neuropathology also develops in the brains of elderly humans, individuals with Alzheimer's disease, and dogs. Both species develop senile plaque neuropathology, with more extensive plaque accumulation associated with severe cognitive impairments. This article discusses similarities in the clinical features and development of neuropathology with age in both dogs and humans and provides a discussion of treatment options.

False

CitationGPTRetr483

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aged companion animals exhibit brain pathologies that mirror those found in humans including plaques tangles vascular cerebral amyloid angiopathy caa myelin disruption lipofuscin neuronal vacuoles axonal degeneration and abnormalities in cholinergic neurons Title of the paper: The canine as an animal model of human aging and dementia. Abstract of the paper: The aged canine displays many features that make it an excellent model for studying the progression of pathology in brain aging and linking these findings to learning, memory and other cognitive functions. Canines develop extensive beta-amyloid deposition within neurons and their synaptic fields, which appears to give rise to senile plaques. These plaques are primarily of the early diffuse subtype. Aged canines also exhibit accumulations of lipofuscin, cerebral vascular changes, dilation of the ventricles, and cytoskeletal changes. Neurofibrillary tangles (NFTs) are not present in the aged canine. Thus, the aged canine brain provides a suitable model for studying early degeneration normally considered to be pre-Alzheimer's. This supposition is also supported by behavioral data. We have found that the extent of beta-amyloid deposition correlates with a decline in select measures of cognitive function. These data provide the first evidence of a correlation between beta-amyloid accumulation and cognitive decline in the absence of NFTs. We summarize four lines of evidence that support using the aged canine as a model of human aging: (a) Aged canines develop aspects of neuropathology similar to that observed in aged humans; (b) Veterinarians have observed that many canines exhibit a clinical syndrome of age-related cognitive dysfunction; (c) Aged canines are deficient on a variety of neuropsychological tests of cognitive function; (d) The level of beta-amyloid accumulation correlates with cognitive dysfunction in the canine. These data indicate that the aged canine is a particularly useful model for studying age-related cognitive dysfunction (ARCD), early neuronal changes associated with aging, and the initial stages of senile plaque formation.

False

CitationGPTRetr484

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aged companion animals exhibit brain pathologies that mirror those found in humans including plaques tangles vascular cerebral amyloid angiopathy caa myelin disruption lipofuscin neuronal vacuoles axonal degeneration and abnormalities in cholinergic neurons Title of the paper: A canine model of human aging and Alzheimer's disease. Abstract of the paper: The aged dog naturally develops cognitive decline in many different domains (including learning and memory) but also exhibits human-like individual variability in the aging process. The neurobiological basis for cognitive dysfunction may be related to structural changes that reflect neurodegeneration. Molecular cascades that contribute to degeneration in the aging dog brain include the progressive accumulation of beta-amyloid (Aβ) in diffuse plaques and in the cerebral vasculature. In addition, neuronal dysfunction occurs as a consequence of mitochondrial dysfunction and cumulative oxidative damage. In combination, the aged dog captures key features of human aging, making them particularly useful for the development of preventive or therapeutic interventions to improve aged brain function. These interventions can then be translated into human clinical trials. This article is part of a Special Issue entitled: Animal Models of Disease.

False

CitationGPTRetr485

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aged companion animals exhibit brain pathologies that mirror those found in humans including plaques tangles vascular cerebral amyloid angiopathy caa myelin disruption lipofuscin neuronal vacuoles axonal degeneration and abnormalities in cholinergic neurons Title of the paper: Age-related changes in the brain of the dog. Abstract of the paper: Although many age-related changes have been described in the nervous system of different species, few authors have specifically studied the topic. Knowledge of such changes is essential to veterinary pathologists, who must distinguish the lesions of specific pathologic processes from those arising as a result of normal aging. The brains of 20 old dogs, ranging in age from 8 to 18 years, were compared with those of 10 young dogs using routine staining techniques (hematoxilin and eosin, periodic acid-Schiff), special staining techniques (periodic acid-methenamine silver stain), and immunohistochemical techniques to detect glial fibrillary acid protein, neurofilaments, ubiquitin, and beta-amyloid. Changes affected meninges and choroid plexuses, meningeal and parenchymal vessels, neurons, and glial cells. Of special interest was the presence of polyglucosan bodies, cerebrovascular amyloid deposition, senile plaques, and ubiquitinated bodies. Some of the age-related changes found, particularly lipofuscin, polyglucosan bodies, and beta-amyloid protein deposition, may play a role in the pathogenesis of the canine cognitive dysfunction syndrome. The dog could be used as a natural animal model for the study of normal aging and human neurodegenerative diseases.

False

CitationGPTRetr486

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aged companion animals exhibit brain pathologies that mirror those found in humans including plaques tangles vascular cerebral amyloid angiopathy caa myelin disruption lipofuscin neuronal vacuoles axonal degeneration and abnormalities in cholinergic neurons Title of the paper: Histopathological and immunohistochemical comparison of the brain of human patients with Alzheimer's disease and the brain of aged dogs with cognitive dysfunction. Abstract of the paper: Alzheimer's disease (AD) is the most common progressive form of dementia in aged people. Microscopical changes in the brains of AD patients include the formation of senile plaques (SPs), neurofibrillary tangles (NFTs) and granulovacuolar degeneration and the deposition of amyloid-beta (Aβ). Aged dogs are known to suffer from cognitive dysfunction and this state is associated with deposition of Aβ in the brain. The aim of the present study was to investigate tau phosphorylation of neurons and astrocytes in the brain of aged dogs with progressive cognitive impairment. Changes in the brain of aged dogs with cognitive dysfunction were compared with those in the brain of patients with AD of Braak stage V. Immunohistochemically, Aβ deposition, phosphorylated tau Ser396 (p-tau Ser396) and ubiquitin were observed in the parietal cortex and hippocampus of aged dogs with cognitive dysfunction. Astrocytes with expression of p-tau Ser396 and neurons with co-localization of p-tau Ser396 and ubiquitin were observed. Expression of p-tau Ser396 and accumulation of ubiquitin were significantly increased in the parietal cortex and dorsal part of the hippocampus of the brain of aged dogs when compared with expression of these molecules in human AD.

True

CitationGPTRetr487

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aged companion animals exhibit brain pathologies that mirror those found in humans including plaques tangles vascular cerebral amyloid angiopathy caa myelin disruption lipofuscin neuronal vacuoles axonal degeneration and abnormalities in cholinergic neurons Title of the paper: Neurobiology of the aging dog. Abstract of the paper: Aged canines naturally accumulate several types of neuropathology that may have links to cognitive decline. On a gross level, significant cortical atrophy occurs with age along with an increase in ventricular volume based on magnetic resonance imaging studies. Microscopically, there is evidence of select neuron loss and reduced neurogenesis in the hippocampus of aged dogs, an area critical for intact learning and memory. The cause of neuronal loss and dysfunction may be related to the progressive accumulation of toxic proteins, oxidative damage, cerebrovascular pathology, and changes in gene expression. For example, aged dogs naturally accumulate human-type beta-amyloid peptide, a protein critically involved with the development of Alzheimer's disease in humans. Further, oxidative damage to proteins, DNA/RNA and lipids occurs with age in dogs. Although less well explored in the aged canine brain, neuron loss, and cerebrovascular pathology observed with age are similar to human brain aging and may also be linked to cognitive decline. Interestingly, the prefrontal cortex appears to be particularly vulnerable early in the aging process in dogs and this may be reflected in dysfunction in specific cognitive domains with age.

False

CitationGPTRetr488

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aged companion animals exhibit brain pathologies that mirror those found in humans including plaques tangles vascular cerebral amyloid angiopathy caa myelin disruption lipofuscin neuronal vacuoles axonal degeneration and abnormalities in cholinergic neurons Title of the paper: Dogs with Cognitive Dysfunction as a Spontaneous Model for Early Alzheimer's Disease: A Translational Study of Neuropathological and Inflammatory Markers. Abstract of the paper: Aged companion dogs with canine cognitive dysfunction (CCD) spontaneously develop varying degrees of progressive cognitive decline and particular neuropathological features correspondent to the changes associated with Alzheimer's disease (AD) in humans. The aim of the present study was to characterize certain aspects of neuropathology and inflammatory markers related to aging and CCD in dogs in comparison with human AD. Fifteen brains from aged dogs with normal cognitive function, mild cognitive impairment, or CCD were investigated and compared with two control brains from young dogs and brain sections from human AD subjects. The neuropathological investigations included evaluation of amyloid-β (Aβ) plaque deposition (N-terminally truncated and pyroglutamyl-modified Aβ included), tau pathology, and inflammatory markers in prefrontal cortex. Cortical Aβ deposition was found to be only of the diffuse subtype as no dense-core or neuritic plaques were found. The Aβ deposition followed a progressive pattern in four maturation stages. Accumulation of the Aβ peptide was also observed in the vessel walls. Both immunohistochemically and biochemically measured levels of Aβ pathology in prefrontal cortex showed a consistent positive correlation to age but not to cognitive deficit severity. No evidence of neurofibrillary tau pathology was found. The level of pro-inflammatory cytokines was generally low and showed no significant association to cognitive status. The findings of the present study support the senescent dog with spontaneous cognitive dysfunction as a valuable non-transgenic model for further investigations of the molecular events involved in the neurodegenerative processes associated with aging and early stage AD, especially the Aβ-related pathology.

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CitationGPTRetr489

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aged companion animals exhibit brain pathologies that mirror those found in humans including plaques tangles vascular cerebral amyloid angiopathy caa myelin disruption lipofuscin neuronal vacuoles axonal degeneration and abnormalities in cholinergic neurons Title of the paper: Pathological studies on cerebral amyloid angiopathy, senile plaques and amyloid deposition in visceral organs in aged dogs. Abstract of the paper: The relationship between cerebral lesions such as amyloid angiopathy or senile plaques and amyloid deposition in the visceral organs were studied in 90 autopsy cases of dogs, 0 to 19-year-old. Cerebral amyloid angiopathy was detected in 28 aged dogs (mean age: 13.7-year-old) and was found mostly in or around the wall of cerebral meningeal arterioles and capillaries of the neocortex. That condition was often accompanied by cerebral hemorrhage in dogs more than 9 years of age. Senile plaques were detected in the neocortex of the brain of 12 dogs (mean age: 13.2-year-old) and classified into 3 subtypes, i.e., "diffuse plaque", "primitive plaque" and "classical plaque". Among those 3 subtypes of senile plaques, amyloid containing plaques were small in number. In the visceral organs of dogs with cerebral amyloid angiopathy, amyloid deposition was found in the vascular walls or connective tissues of small intestines at a high frequency and sometimes in the vascular walls of the heart, lung, liver and thyroid gland as well as in atrioventricular valves. Amyloid in both cerebral and visceral organs was congophilic and showed green birefringence under poralized light even after potassium permanganate oxidation.

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CitationGPTRetr490

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aged companion animals exhibit brain pathologies that mirror those found in humans including plaques tangles vascular cerebral amyloid angiopathy caa myelin disruption lipofuscin neuronal vacuoles axonal degeneration and abnormalities in cholinergic neurons Title of the paper: The canine (dog) model of human aging and disease: dietary, environmental and immunotherapy approaches. Abstract of the paper: Aged dogs (beagles) develop losses in executive function, learning and memory. The severity of decline in these cognitive domains represents a spectrum that captures normal aging, mild cognitive impairment and early/mild Alzheimer's disease (AD) in humans. In parallel, dogs naturally accumulate several types of neuropathology (although not all) consistent with human brain aging and AD including cortical atrophy, neuron loss, loss of neurogenesis, amyloid-beta (Abeta) plaques, cerebral amyloid angiopathy and oxidative damage. Many of these neuropathological features correlate with the extent of cognitive decline in a brain region-dependent manner. Dogs are ideally suited for longitudinal studies, and we provide a summary of the beneficial effects of an antioxidant diet, behavioral enrichment, and Abeta immunotherapy. In addition, combinatorial treatment approaches can be a powerful strategy for improving brain function through enhancement of multiple molecular pathways.

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CitationGPTRetr491

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aged companion animals exhibit brain pathologies that mirror those found in humans including plaques tangles vascular cerebral amyloid angiopathy caa myelin disruption lipofuscin neuronal vacuoles axonal degeneration and abnormalities in cholinergic neurons Title of the paper: Dogs with cognitive dysfunction syndrome: a natural model of Alzheimer's disease. Abstract of the paper: In the search for appropriate models for Alzheimer's disease (AD) involving animals other than rodents, several laboratories are working with animals that naturally develop cognitive dysfunction. Among the animals tested, dogs are quite unique in helping to elucidate the cascade of events that take place in brain amyloid-beta (Aβ)deposition aging, and cognitive deficit. Recent innovative research has validated human methods and tools for the analysis of canine neuropathology and has allowed the development of two different approaches to investigate dogs as natural models of AD. The first approach relates AD-like neuropathy with the decline in memory and learning ability in aged housed dogs in a highly controlled laboratory environment. The second approach involves research in family-owned animals with cognitive dysfunction syndrome. In this review, we compare the strengths and limitations of housed and family-owned canine models, and appraise their usefulness for deciphering the early mechanisms of AD and developing innovative therapies.

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CitationGPTRetr492

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aged companion animals exhibit brain pathologies that mirror those found in humans including plaques tangles vascular cerebral amyloid angiopathy caa myelin disruption lipofuscin neuronal vacuoles axonal degeneration and abnormalities in cholinergic neurons Title of the paper: Neuropathology of Aging in Cats and its Similarities to Human Alzheimer's Disease. Abstract of the paper: Elderly cats develop age-related behavioral and neuropathological changes that ultimately lead to cognitive dysfunction syndrome (CDS). These neuropathologies share similarities to those seen in the brains of humans with Alzheimer's disease (AD), including the extracellular accumulation of ß-amyloid (Aβ) and intraneuronal deposits of hyperphosphorylated tau, which are considered to be the two major hallmarks of AD. The present study assessed the presence and distribution of Aβ and tau hyperphosphorylation within the cat brain (n = 55 cats), and how the distribution of these proteins changes with age and the presence of CDS. For this, immunohistochemistry was performed on seven brain regions from cats of various ages, with and without CDS (n = 10 with CDS). Cats accumulate both intracytoplasmic and extracellular deposits of Aβ, as well as intranuclear and intracytoplasmic hyperphosphorylated tau deposits. Large extracellular aggregates of Aβ were found in elderly cats, mainly in the cortical brain areas, with occasional hippocampal aggregates. This may suggest that these aggregates start in cortical areas and later progress to the hippocampus. While Aβ senile plaques in people with AD have a dense core, extracellular Aβ deposits in cats exhibited a diffuse pattern, similar to the early stages of plaque pathogenesis. Intraneuronal Aβ deposits were also observed, occurring predominantly in cortical brain regions of younger cats, while older cats had few to no intraneuronal Aβ deposits, especially when extracellular aggregates were abundant. Intracytoplasmic hyperphosphorylated tau was found within neurons in the brains of elderly cats, particularly in those with CDS. Due to their ultrastructural features, these deposits are considered to be pre-tangles, which are an early stage of the neurofibrillary tangles seen in AD. The largest numbers of pre-tangles are found mainly in the cerebral cortex of elderly cats, whereas lower numbers were found in other regions (i.e., entorhinal cortex and hippocampus). For the first time, intranuclear tau was found in both phosphorylated and non-phosphorylated states within neurons in the cat brain. The highest numbers of intranuclear deposits were found in the cortex of younger cats, and this tended to decrease with age. In contrast, elderly cats with pre-tangles had only occasional or no nuclear labelling.

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CitationGPTRetr493

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aged companion animals exhibit brain pathologies that mirror those found in humans including plaques tangles vascular cerebral amyloid angiopathy caa myelin disruption lipofuscin neuronal vacuoles axonal degeneration and abnormalities in cholinergic neurons Title of the paper: Animal models of Alzheimer's disease and evaluation of anti-dementia drugs. Abstract of the paper: Alzheimer's disease (AD) is the most common cause of progressive decline of cognitive function in aged humans, and is characterized by the presence of numerous senile plaques and neurofibrillary tangles accompanied by neuronal loss. Some, but not all, of the neuropathological alterations and cognitive impairment in AD can be reproduced genetically and pharmacologically in animals. It should be possible to discover novel drugs that slow the progress or alleviate the clinical symptoms of AD by using these animal models. We review the recent progress in the development of animal models of AD and discuss how to use these model animals to evaluate novel anti-dementia drugs.

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CitationGPTRetr494

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aged companion animals exhibit brain pathologies that mirror those found in humans including plaques tangles vascular cerebral amyloid angiopathy caa myelin disruption lipofuscin neuronal vacuoles axonal degeneration and abnormalities in cholinergic neurons Title of the paper: β-amyloid and tau pathology in the aging feline brain. Abstract of the paper: Domestic cats (Felis catus) are known to develop cognitive impairment, and several small series have demonstrated both β-amyloid and tau aggregation, including neurofibrillary tangles, with age, making them a promising physiologic model of Alzheimer disease (AD). We therefore report the largest feline autopsy cohort to date of 32 cats ranging from 1.5 to 22.1 years of age, with systematic neuropathologic assessment according to NIA-Alzheimer's Association Criteria. Formalin-fixed paraffin-embedded tissue sections of brain were obtained retrospectively from cats autopsied at the Iowa State College of Veterinary Medicine. We found β-amyloid staining, predominantly in Cortical Layers IV and VI in 27 of the 32 cats used in the study, with four of these animals showing tau-positive tangles and neuropil threads. In 75% of these cases (3/4), tau deposition was limited to entorhinal cortex, while one case showed diffuse positive staining throughout the hippocampal formation and neocortex. This last case showed positive staining for all phospho-tau-specific antibodies tested, similar to the pattern seen in human AD. Interestingly, we saw a higher ratio of pretangles to tangles than that in human AD, and none of the cases showed neuritic plaques on any of the stains used. Our findings indicate that aging domestic cats spontaneously develop both β-amyloid and tau pathology similar, but not identical to that seen in human AD. This suggests that the domestic cat may serve as a potential model for mechanistic and therapeutic AD studies, but that additional research is needed to identify differences between the neuropathology of aging in humans and felines.

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CitationGPTRetr495

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aged companion animals exhibit brain pathologies that mirror those found in humans including plaques tangles vascular cerebral amyloid angiopathy caa myelin disruption lipofuscin neuronal vacuoles axonal degeneration and abnormalities in cholinergic neurons Title of the paper: Beta-amyloid accumulation in aged canine brain: a model of early plaque formation in Alzheimer's disease. Abstract of the paper: We characterized eight aged beagles (maintained from birth in a laboratory colony) and one black Labrador using Bielschowsky's, thioflavine S, and Congo red staining, and antibodies to the beta-amyloid peptide, dystrophic neurites, and other plaque components. All plaques within these canine brains were of the diffuse subtype and were neither thioflavine S- nor Congo red-positive. The majority of plaques in the entorhinal cortex contained numerous neurons within them while plaques in the dentate gyrus did not. beta-Amyloid immunoreactivity was also present within select neurons and neuronal processes and was detected as a diffuse linear zone corresponding to the terminal fields of the perforant path. There was no significant correlation between extent of beta-amyloid accumulation and neuron number in entorhinal cortex. Neither tau-1, PHF-1, nor SMI-31-immunostaining revealed dystrophic fibers, confirming the classification of these plaques as diffuse. Canine plaques did not appear to contain bFGF- or HS-positive immunostaining. This may explain why neuritic involvement was not detected within these canine plaques. It is possible that the beta-amyloid within the canine brain has a unique primary structure or may not be in an assembly state that adversely affects neurons.

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CitationGPTRetr496

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aged companion animals exhibit brain pathologies that mirror those found in humans including plaques tangles vascular cerebral amyloid angiopathy caa myelin disruption lipofuscin neuronal vacuoles axonal degeneration and abnormalities in cholinergic neurons Title of the paper: The domestic cat as a natural animal model of Alzheimer's disease. Abstract of the paper: INTRODUCTION Alzheimer's disease (AD) is the most dominant neurodegenerative disorder that causes dementia, and no effective treatments are available. To study its pathogenesis and develop therapeutics, animal models representing its pathologies are needed. Although many animal species develop senile plaques (SP) composed of amyloid-β (Aβ) proteins that are identical to those found in humans, none of them exhibit neurofibrillary tangles (NFT) and subsequent neurodegeneration, which are integral parts of the pathology of AD. RESULTS The present study shows that Aβ accumulation, NFT formation, and significant neuronal loss all emerge naturally in the hippocampi of aged domestic cats. The NFT that form in the cat brain are identical to those seen in human AD in terms of their spatial distribution, the cells they affect, and the tau isoforms that comprise them. Interestingly, aged cats do not develop mature argyrophilic SP, but instead accumulate intraneuronal Aβ oligomers in their hippocampal pyramidal cells, which might be due to the amino acid sequence of felid Aβ. CONCLUSIONS These results suggest that Aβ oligomers are more important than SP for NFT formation and the subsequent neurodegeneration. The domestic cat is a unique animal species that naturally replicates various AD pathologies, especially Aβ oligomer accumulation, NFT formation, and neuronal loss.

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CitationGPTRetr497

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aged companion animals exhibit brain pathologies that mirror those found in humans including plaques tangles vascular cerebral amyloid angiopathy caa myelin disruption lipofuscin neuronal vacuoles axonal degeneration and abnormalities in cholinergic neurons Title of the paper: Ageing changes in cat brains demonstrated by beta-amyloid and AT8-immunoreactive phosphorylated tau deposits. Abstract of the paper: The life expectancy of domestic pet cats is increasing, along with the occurrence of geriatric-onset behavioural problems, such as cognitive dysfunction syndrome (CDS). While the cause of CDS is unclear, it has been suggested that it may result from age-related neurodegeneration. In aged and in particular senile human beings, histopathological changes may include the extracellular accumulation of plaque-like deposits of beta-amyloid (Abeta) protein and the intracellular accumulation of an abnormally hyperphosphorylated form of the microtubule-associated protein, tau. In severe cases, the latter may form into neurofibrillary tangles. Brain material was assessed from 19 cats, aged from 16 weeks to 14 years; 17 of which had clinical signs of neurological dysfunction. Immunohistochemical methods were used to detect Abeta and its intracellular precursor protein (amyloid precursor protein (APP)) and hyperphosphorylated-tau. APP was constitutively expressed, with diffuse staining of neurons and blood vessels being detected in all cats. More intense staining and diffuse extracellular Abeta staining deposits were found within the deep cortical areas of the anterior- and occasionally mid-cerebrum of seven cats, all of which were over 10 years of age. Neurons staining intensely positive for AT8-immunoreactivity were seen in two cats, aged 11 and 13 years. However, no mature neurofibrillary tangles were detected. This study demonstrated that extracellular Abeta accumulation and AT8-immunoreactivity within neurons are age-related phenomena in cats, and that they can occur concurrently. There are similarities between these changes and those observed in the brains of aged people and other old mammals.

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CitationGPTRetr498

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aged companion animals exhibit brain pathologies that mirror those found in humans including plaques tangles vascular cerebral amyloid angiopathy caa myelin disruption lipofuscin neuronal vacuoles axonal degeneration and abnormalities in cholinergic neurons Title of the paper: Immunohistochemical investigation of the brain of aged dogs. I. Detection of neurofibrillary tangles and of 4-hydroxynonenal protein, an oxidative damage product, in senile plaques. Abstract of the paper: In the aging dog brain lesions develop spontaneously. They share some morphological characteristics with those of Alzheimer 's disease in man. Diffuse and primitive plaques are well known, whereas neuritic plaques rarely develop. Neurofibrillary tangles have not been seen in the canine. The aim of the present investigation was to study major age-related changes of the dog's brain using paraffin sections with respect to cross-immunoreactivity of tau, A beta protein and other immunoreactive components including hydroxynonenal protein, which is a marker for oxidative damage. The occurrence of neurofibrillary tangles and of the protein tau therein was studied in serial brain sections of two dogs with the Gallyas stain and by immunohistochemistry with three different antibodies against tau. Senile plaques were stained with a monoclonal anti-A beta (residues 8-17), polyclonal anti-apolipoprotein E and a monoclonal antibody against 4-hydroxynonenal (HNE). Amyloid deposits and controls were screened by Congo red staining viewed in fluorescent light, followed by polarized light for green birefringence. With the Gallyas stain and one of the antisera against tau, neurofibrillary tangles were revealed in a similar dispersed pattern, whereas the other antitau antisera gave negative results. With the anti-HNE a positive reaction was found in cerebral amyloid deposits and in vascular wall areas where amyloid deposition was confirmed by Congo-red staining, and in perivascular cells and in some neurons. These results indicate that the canine with his tangles and plaques which show oxidative changes, forms a spontaneous modelfor understanding the early changes and their interrelationships in Alzheimer's disease.

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CitationGPTRetr499

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aged companion animals exhibit brain pathologies that mirror those found in humans including plaques tangles vascular cerebral amyloid angiopathy caa myelin disruption lipofuscin neuronal vacuoles axonal degeneration and abnormalities in cholinergic neurons Title of the paper: Bridging the Gap between Alzheimer's Disease and Alzheimer's-like Diseases in Animals. Abstract of the paper: The average life span steadily grows in humans and in animals kept as pets or left in sanctuaries making the issue of elderly-associated cognitive impairment a hot-spot for scientists. Alzheimer's disease (AD) is the most prevalent cause of progressive mental deterioration in aging humans, and there is a growing body of evidence that similar disorders (Alzheimer's-like diseases, ALD) are observed in animals, more than ever found in senescent individuals. This review reveals up to date knowledge in pathogenesis, hallmarks, diagnostic approaches and modalities in AD faced up with ALD related to different animal species. If found at necropsy, there are striking similarities between senile plaques (SP) and neurofibrillary tangles (NFT) in human and animal brains. Also, the set of clinical symptoms in ALD resembles that observed in AD. At molecular and microscopic levels, the human and animal brain histopathology in AD and ALD shows a great resemblance. AD is fatal, and the etiology is still unknown, although the myriad of efforts and techniques were employed in order to decipher the molecular mechanisms of disease onset and its progression. Nowadays, according to an increasing number of cases reported in animals, apparently, biochemistry of AD and ALD has a lot in common. Described observations point to the importance of extensive in vivo models and extensive pre-clinical studies on aging animals as a suitable model for AD disease.

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