bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted Multiplexed MALDI MS Platform Enables Detection of Novel Pathogenic Forms of Tau, Amyloid Beta and Alpha Synuclein
Authors: Bergo Vladislav 
Published: January 2025

AbstractBackgroundThe rapidly growing pipeline of target‐specific Alzheimer’s Disease (AD) therapeutic candidates requires accompanying tests that can identify patients likely to have a beneficial response. The growing importance of multiple pathologies in determining AD progression and treatment response underscores this need. Our work focuses on establishing analytical capability to expand detectable forms of major protein drug targets for AD: Tau, amyloid beta (Ab) and a‐Synuclein (aS) proteoforms as potential personalized molecular signatures.MethodNovel analytical workflow (BAMS™) based on single bead immunoaffinity capture, enrichment and mass spectrometry (MS) quantification was applied to measure distinct species of CSF Tau, Aβ and αS. Samples from cognitively normal (CN) and AD subjects were acquired from a biobank and measured either non‐digested or after digestion with LysC protease. MS data was collected on Bruker Autoflex Max MALDI TOF instrument and processed using in‐house developed software.ResultBAMS™ has detected >40 CSF Aβ peptides, comprising N‐terminal AβX‐40/42 (X= 1, 3, 5, 7, 10, 11) and C‐terminal Aβ1‐X (X between 6 – 43) truncation series. The latter included previously unreported peptides Aβ1‐6‐Aβ1‐11, Aβ1‐21‐Aβ1‐26, Aβ1‐31 and Aβ1‐32. Many peptides including amyloid plaque pathology markers Aβ1‐40 and Aβ1‐42 were measured with CVs under 10%. A survey of CN and AD subjects reveals major differences within Aβ1‐X patterns likely reflecting different amyloid metabolism. Total and phospho‐Tau (tTAU and pTAU) probes revealed extensive endogenous proteolysis in the Proline Rich Domain with multiple detected fragments terminating at distinct proline sites. The pTAU probe detected hyperphosphorylated sequences containing up to 3 and 5 modified sites in CN and AD, respectively, which unambiguously differentiated normal from diseased samples. Three αS probes have been developed that measure: (1) total protein abundance, (2) C‐terminal fragmentation and (3) relative abundance of monomer and dimer species of isoforms SNCA140, SNCA126 and SNCA112.ConclusionHealthy and diseased human CSF may contain a wider range of Tau, Aβ and αS proteoforms than previously recognized. BAMS™ can simultaneously measure multiple protein targets and multiple proteoforms via independent probing of distinct protein regions. The broad sequence coverage enables screening of multiple biomarker candidates for accurate molecular profiling of tau tangles, amyloid plaques and Lewy bodies.
Survival and time till nursing home admission in persons with dementia: a systematic review and meta‐analysis
Authors: Brück Chiara C. , Mooldijk Sanne S. , Kuiper Lieke M. , Wolters Frank J. 
Published: January 2025

AbstractBackgroundAccurate prognosis after a dementia diagnosis is important for patient information and advanced care planning, but available information is fragmented, with inconsistent estimates that are often restricted to survival. We aimed to summarise the literature to assess survival times and time to nursing home after dementia diagnosis and determine the impact of clinical characteristics and study design.MethodWe systematically searched MEDLINE and EMBASE for studies reporting time from dementia diagnosis to nursing home admission or death. Two reviewers independently extracted information on study design, patient population, disease characteristics, and outcomes, including semi‐automated quantification of Kaplan‐Meier survival curves. We used a modified Newcastle‐Ottawa Scale for study appraisal and performed meta‐regression analyses to identify determinants of prognosis.ResultOf 212 included studies, 188 reported on survival (1,255,916 participants) and 70 on nursing home admission (229,925 participants). Overall, median survival was 4.7 years (interquartile range: 3.4‐6.0), and this differed substantially with patient demographics and disease characteristics. Survival varied with age and was on average 6.6 years among studies with a median age of 65 years, and 3.7 years with a median age of 85 (Figure 1A). Shorter observed survival among women than men was explained entirely by later disease onset in women. Survival was longer among patients with Alzheimer’s disease compared to all‐cause dementia (Figure 2), and longer in more recent studies (1.3 years comparing studies ≥2010 to <1990). Patients in Asia lived longer after diagnosis than their counterparts in the U.S. and Europe (1.1‐ and 1.3‐years difference, respectively). Survival probabilities were 88%, 69%, 52% and 26% after 1, 3, 5 and 10 years of follow‐up, respectively (Figure 3A). Taken together, variation in methodology and clinical characteristics explained 50% of heterogeneity in survival among studies. Median time to nursing home admission was 3.3 years (IQR 2.2‐4.0; Figure 1B), with 15% of patients being admitted after 1 year, increasing to 36% at 3, and 57% at 5 years from diagnosis (Figure 3B), which was influenced only by age.ConclusionPatients with dementia have an average life‐expectancy of five years at time of diagnosis, of which two years are lived in nursing homes.
The incidence of all‐cause dementia and Alzheimer’s disease from around the world: data from the COSMIC collaboration
Authors: Vella Ashleigh S. , Visontay Rachel , Lipnicki Darren M. , Nichols Emma , Steinmetz Jamie , Lipton Richard B. , Llibre‐Rodriguez Juan J. , Katz Mindy J. , Scarmeas Nikolaos , Guerchet Maëlenn , Preux Pierre‐Marie , Ritchie Karen , Carriere Isabelle , Petersen Maria Skaalum , Skoog Ingmar , Rolandi Elena , Kim Ki Woong , Riedel‐Heller Steffi G. , Shahar Suzana , Ganguli Mary , Anstey Kaarin J. , Lobo Antonio , Crawford John D. , Mewton Louise , Sachdev Perminder S. ,   other COSMIC authors
Published: January 2025

AbstractBackgroundHigh‐income countries (HICs) are over‐represented in current global dementia incidence rates, skewing estimates. Variance in diagnostic methods between HICs and low‐ and middle‐income countries (LMICs) is speculated to contribute to the regional differences in rates. Cohort Studies of Memory in an International Consortium (COSMIC) offers a unique opportunity to address these research inequalities by harmonising data from international studies, including representation from LMICs. This study aimed to identify dementia incidence rates by age and sex in various regions worldwide, where data for dementia diagnosis were available.MethodData were obtained from 36 members of COSMIC, representing 28 countries across 6 continents (HICs: Australia, Canada, Faroe Islands, France, Germany, Greece, Italy, Japan, Netherlands, South Korea, Spain, Sweden, & USA; LMICs: Brazil, China, Cuba, Dominican Republic, Ecuador, Indonesia, Malaysia, Mexico, Nigeria, Peru, Philippines, Republic of Congo, & Tanzania). For each member study, we calculated incidence rates for all‐cause dementia. Findings from 14 studies, with a consensus diagnosis are presented in the results. Using an Item Response Theory approach, we are currently calculating a comparable incidence rate for those studies without a consensus diagnosis.ResultConsistent with previous trends, incidence rates (per 100 person‐years) increased with age, from 65‐70 years‐old to 85‐90 years‐old, for both males (i.e., Republic of Congo, 4.41 to 19.57; France, 0.46 to 3.89; USA, 0.17 to 3.22; Spain, 0.31 to 4.22; 65‐70 & 85‐90 cohorts respectively) and females (i.e., Republic of Congo, 3.57 to 15.31; France, 0.45 to 3.72; USA, 0.22 to 4.25; Spain, 0.36 to 4.96; 65‐70 & 85‐90 cohorts respectively). There were no sex differences in incidence rates in younger age groups (60‐65). Among older age groups, however, women tended to have higher incidence rates than men, in some countries (Faroe Islands, Germany, Sweden, and USA).ConclusionGeographical differences in dementia incidence rates likely represent inherent variation among countries, beyond methodological considerations. We are working to expand the range of studies and regions for which we calculate dementia incidence rates. This involves the development of approaches to classify and harmonise incident dementia in studies lacking consensus diagnoses. Doing so will bolster LMIC representation.
The Common Marmoset as a Preclinical Primate Model for Alzheimer’s disease
Authors: Silva Afonso C 
Published: January 2025

AbstractBackgroundOur limited understanding of the mechanisms that trigger the emergence of Alzheimer’s disease (AD) has contributed to the lack of interventions that stop, prevent, or fully treat this disease. We believe that developing a nonhuman primate model of AD will be an essential step toward overcoming the limitations of other model systems and is crucial for investigating primate‐specific mechanisms underlying the cellular and molecular root causes of the pathogenesis and progression of AD.MethodThe consortium successfully generated viable founders carrying PSEN1 mutations. in C410Y and A426P using CRISPR/Cas9 approaches, with germline transmission demonstrated in the C410Y line. Longitudinal characterization of these models, their germline offspring, and normal aging outbred marmosets is ongoing. All data and resources from this consortium will be shared with the greater AD research community.ResultThe consortium successfully generated viable founders carrying PSEN1 mutations. in C410Y and A426P using CRISPR/Cas9 approaches, with germline transmission demonstrated in the C410Y line. Longitudinal characterization of these models, their germline offspring, and normal aging outbred marmosets is ongoing. All data and resources from this consortium will be shared with the greater AD research community.ConclusionBy establishing marmoset models of AD, we will be able to investigate primate‐specific cellular and molecular root causes that underlie the pathogenesis and progression of AD, overcome limitations of other model organisms, and support future translational studies to accelerate the pace of bringing therapies to patients.
Deciphering the Protective Interplay between Cancer and Alzheimer’s: Advancing Drug Repositioning Strategies for Alzheimer’s Disease Treatment
Authors: Zhao Hong , Vasquez Matthew , Ahn Ju Young , Dong Wenjuan , Sheng Jianting , Yin Zheng , Wong Stephen T.C. 
Published: January 2025

AbstractBackgroundGlobal epidemiological studies involving over nine million participants have shown a 35% lower incidence of Alzheimer’s Disease (AD) in older cancer survivors compared to those without a history of cancer. This inverse relationship, consistent across recent studies with methodological controls, suggests that cancer itself, rather than cancer treatments, may offer protective factors against AD. This insight opens avenues for novel therapeutic strategies targeting early AD by harnessing cancer‐associated protective factors.MethodsTo investigate the potential protective effect of cancer against Alzheimer’s Disease (AD), we developed “cancer‐in‐AD” mouse models. These models involved injecting a small number of breast cancer cells into young AD‐model mice (5xFAD) and monitoring amyloid plaque progression. Additionally, we introduced extracellular vesicles (EVs) from breast tumor‐bearing mice into similar AD models. Using spatial transcriptomics, we analyzed brain tissue gene expression and cell‐cell interactions, focusing on the astrocyte‐microglia‐oligodendrocyte network near amyloid plaques. This approach helped identify potential drugs for repurposing in AD treatment.ResultsThe study found a significant reduction in amyloid burden within the brains of the cancer‐in‐AD mouse models compared to age‐matched cancer‐free AD mice. The administration of EVs from cancer animal’s plasma to the AD mice prompted the release of various inflammatory cytokines and chemokines. A key discovery was an activated astrocyte‐microglia‐oligodendrocyte signaling network that regulates amyloid‐beta homeostasis in these mouse brains. Out of 49 FDA‐approved drugs identified to induce this cancer‐induced signaling, 11 showed promise in improving AD symptoms and reducing amyloid and tau accumulations, in both preclinical and clinical studies.ConclusionsThe study reveals a notable decrease in amyloid levels in AD mice with cancer or exposed to tumor‐derived EVs, linked to immune system reprogramming and glial network activation. This supports the study’s drug repositioning approach and sets the stage for further research into the anti‐AD properties of these drugs, focusing on identifying crucial signaling elements for enhanced drug repositioning and combination treatment strategies.
Social Condition and Cognitive Function Among Boston Area Puerto Ricans
Authors: Palacios Natalia , Ekaterina Shishova , Scott Tammy , Falcon Luis , Tucker Katherine L 
Published: January 2025

AbstractBackgroundThis study aimed to assess associations between socioeconomic condition and cognitive function among Puerto Rican adults residing in the greater Boston Area.MethodsWe assessed the relationship between a score of social condition, encompassing education, income‐to‐poverty ratio, perceived stress, food security, and psychological acculturation, and cognitive function in a cohort of Puerto Rican Adults residing in the greater Boston area. The score was assessed over more than 12 years of follow‐up and ranged from 0 (best social condition) to 15 (poorest social condition). We examined the varying contributions of traditional (education and income) vs. psychosocial (perceived stress, food security, and psychological acculturation) in relation to cognitive function.ResultsAfter adjusting for covariates, poorer 12‐year average social condition was associated with poorer cognitive function (β = ‐ 0.52, 95% CI = [‐ 0.66, ‐ 0.38; P trend = 5.7×10−14 for highest vs. lowest disparity category). The association was stronger for traditional (β = ‐ 0.53, 95% CI = [‐ 0.67, ‐ 0.40] P trend = 5.7×10−14) than psychosocial (β = ‐0.20, 95% CI = [‐ 0.34, ‐ 0.06] P trend = 0.05) measures, but both were significantly associated with cognitive function.ConclusionsOur findings in US‐mainland Puerto Rican adults suggest that socioeconomic condition, both traditional and psychosocial, are associated with cognitive function. This work highlighting the importance of addressing and reducing social disparities to promote better cognitive health outcomes.
The role of volunteer older adults in the exercise programme of the Comprehensive Resilience‐Building Psychosocial Intervention (CREST) for people with dementia
Authors: Casey Dympna , Smyth Siobhán , Doyle Priscilla , Gallagher Niamh , Whelan Barbara 
Published: January 2025

AbstractBackgroundThe CREST intervention included three components one of which was an eight‐week exercise programme. The aim of the programme was to increase the exercise capacity of people with mild to moderate dementia and facilitate social engagement with volunteer older adults from the community supporting a person with dementia, raising awareness and understanding of dementia. We explore the experience of volunteer older adults’ participation in the exercise component of the CREST intervention following a five‐hour training on dementia awareness and the CREST exercise programme.MethodQualitative semi‐structured focus groups and individual interviews were conducted with the older adults, people with dementia, their carers and the facilitators of the exercise programme. Data were analysed thematically. Older adults also completed the Dementia Attitude Scale (DAS) and the Dementia Knowledge Twenty (DK‐20) questionnaire pre‐ and post‐intervention.ResultOverall, the older adults (n = 9), people with dementia (n = 9), their carers (n = 9) and the programme facilitators (n = 2) were positive about the inclusion of the older adults in the exercise programme. Most commented on the role of the older adults in encouraging and supporting the people with dementia with the exercises and the social aspect. Two of the people with dementia highlighted difficulties in personality but they found a way to work together as the weeks progressed. While the majority of older adults felt that the training they received prior to the intervention prepared them sufficiently to support the person with dementia, there were only slight improvements in attitudes and knowledge scores about dementia based on the DAS (baseline M = 105; SD = 9.68; post‐intervention M = 109; SD = 8.80) and DK‐20 (baseline M = 11.3; SD = 4.74; post‐intervention M = 14.2; SD = 2.59).ConclusionThe volunteer older adults actively contributed to the exercise program, providing encouragement and support to the people with dementia, and enhancing the social dynamics of the sessions. There were modest improvements in the attitudes and knowledge scores about dementia among the volunteer older adults, suggesting a potential positive impact of the intervention on their awareness and understanding.
Development of a Dementia Intensive Advanced Practice Provider Fellowship
Authors: Arthur Anne K , Gillen Lindsey , Fikru Samantha , Malcolm Jessica , Vidoni Eric D 
Published: January 2025

AbstractBackgroundThe aging population is driving an unprecedented increase in the number of individuals with Alzheimer’s disease and related dementias (AD/ADRD). Currently, there is limited availability of specialists in AD/ADRD and a growing need in the United States for new access points to treat the estimated 7.2 million people with AD/ADRD expected in 2025. Care access disparities are particularly apparent in the Central Plains states, most of which are considered “Neurology Deserts”. In response, the University of Kansas has developed an Advanced Practice Provider (APP) Brain Health Fellowship to increase sustainable access to AD/ADRD care.MethodsThe KU Alzheimer’s Disease Research Center (KU ADRC) and the KU School of Nursing developed a 6‐month AD/ADRD fellowship to train APPs to recognize, diagnose and treat AD/ADRD. Learning modules and rotations were selected by an expert panel, including our neurology and APP clinical fellowship directors, and cover relevant topics and departments encountered during the diagnosis and treatment of AD/ADRD. Examples include AD/ADRD treatments, neuropsychology, neuroimaging, biomarkers, social work support, end of life care planning, and research. The weekly schedule includes didactics, precepted clinics, mentored clinics, and specialty clinics. The program director and fellow review evaluations, clinical progress, and career planning monthly. The fellow completes pre‐ and post‐fellowship competence and dementia knowledge surveys developed by the program. The fellow receives a competitive salary, laptop, and education materials.ResultsTo date, one fellow has completed the program. Pre‐ and post‐test results showed an 85% increase in AD/ADRD knowledge. The fellow, on average, rated the preceptors and program at “Above Average” to “Excellent”. Feedback during and after the fellowship has been incorporated into ongoing programming. The first fellow was hired by the KU ADRC.ConclusionsThe KU ADRC APP Brain Health Fellowship is a first‐of‐its‐kind approach to develop clinicians trained to care for the growing number of individuals with AD/ADRD. Our preliminary results suggest the fellow increased AD/ADRD care competence and the program was valued by the fellow. The immediate post‐program employment of the fellow is evidence of potential benefit to increasing access to care. The fellowship will continue in 2024 and train two more fellows.
Accurate diagnosis of Alzheimer’s disease using specific volatile organic compounds from breath
Authors: Shen Lu , Zhang Sizhe , Liu Haokun , Ouyang Ziyu , Xu Tianyan , Yang Qijie , Zhu Yuan , Wan Meidan , Xiao Xuewen , Yang Xuan , Yuan Li , Bei Yuzhang , Wang Junling , Guo Jifeng , Chen Haibin , Tang Beisha , Jiao Bin 
Published: January 2025

AbstractBackgroundExisting biomarkers including cerebrospinal fluid and positron emission tomography for Alzheimer’s disease (AD) diagnosis are relatively invasive and expensive. Application of exhaled breath collection and volatile organic compound (VOC) detection for AD diagnosis remains unclear.MethodIn this cross‐sectional study, high‐pressure photon ionization time‐of‐flight mass spectrometry (HPPI‐ToF‐MS) was used to detect VOCs from breath in three datasets and patients diagnosed as Parkinson’s disease (PD). Plasma p‐tau181 was quantified using ultra‐sensitive Simoa technology. GC x GC TOF‐MS was used to detect VOCs in plasma. Near‐infrared spectroscopy was carried out to elucidate alterations of brain metabolism.ResultA total of 861 participants were enrolled. Patients with AD were diagnosed according to the 2011 NIA‐AA diagnosis criteria and further confirmed in dataset 1 (n=30) based on the A+T+N+ framework. Datasets 1 and 2 were used to recognize the different VOCs between patients with AD and controls. The diagnostic power of VOCs for AD was confirmed separately in train datasets 1 and 2 and independent test dataset 3. The specific VOCs in AD diagnosis were further compared with patients with PD. Among all participants, no statistical difference was observed in demographic characteristics for dataset 1. Six VOCs, including ethanol (m/z = 46), isopropanol (m/z = 60), chloroethane (m/z = 64), pyrrole/3‐butenenitrile (m/z = 67), 1‐butanol (m/z = 74), and benzene (m/z = 78), were significantly different between the two groups in dataset 1 and were verified in dataset 2 and dataset 3. Ethanol (m/z=46) and pyrrole/3‐butenenitrile (m/z=67) presented areas under the ROC curve (AUCs) values of 0.907 and 0.895, respectively, in datasets 1 and 2 and 0.849 and 0.974, respectively, in dataset 3 (community). The six VOCs were associated with cognitive decline as reflected by neuropsychological tests, five (m/z = 46, 64, 67, 74, and 78) were correlated with plasma p‐tau181 levels, and five (m/z = 46, 60, 67, 74, and 78) showed consistent alteration in plasma. Moreover, five (m/z = 46, 60, 67, 74, and 78) were associated with altered brain connectivity.ConclusionSpecific breath VOCs may be used as simple biomarkers for AD detection.
Investigating the APOE4‐associated heterogeneity of imaging biomarkers across AD diagnostic stages
Authors: Mares Jason , Sharma Anurag , Guo Jia , Nuriel Tal 
Published: January 2025

AbstractBackgroundCarriers of the apolipoprotein E ε4 (APOE4) allele are at an increased risk of developing Alzheimer’s disease (AD) and display an earlier age of onset compared to non‐carriers who develop the disease. While researchers have extensively characterized the impact of APOE4 on the susceptibility of AD, little is known about the differences in disease etiology and presentation in APOE4 carriers vs. non‐carriers.MethodIn order to investigate these differences, we performed a broad analysis of imaging biomarkers in APOE4 carriers vs. non‐carriers present in the ADNI cohort.ResultWe observed differences between APOE4 carriers vs. non‐carriers in several imaging readouts, including Ab‐PET, Tau‐PET, FDG‐PET, and structural MRI measures. These differences were variable based on sex and amyloid positivity. Interestingly, when we compared cognitively normal ADNI participants who converted to MCI or AD to those who did not, we observed APOE4‐dependent differences that may point to specific pathologies that mediate MCI/AD conversion in APOE4 carriers vs. non‐carriers.ConclusionThese observations of pathological heterogeneity between APOE4 carriers vs. non‐carriers reveal significant differences in disease pathogenesis between these two groups, which may have important implications with regard to the diagnosis and treatment of AD in different genetic cohorts.