bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebrospinal fluid proteomics identifies biomarkers for discriminating amyloid PET and tau PET stages
Authors: Wang Zhibo , Chen Yuhan , Jia Jianping 
Published: January 2025

AbstractBackgroundStaging Alzheimer's disease pathology is critical for therapeutic trials and prognosis. Disease staging with amyloid and tau PET provides high accuracy, but this would be more practical with fluid biomarkers. However, current fluid biomarkers are deficient in tracking specific disease stages, especially in advanced stages.MethodParticipants (N=115) were enrolled from the Alzheimer’s Disease Neuroimaging Initiative who had available CSF proteomics and amyloid and tau PET. The proteomic analysis involved approximately 6000 unique CSF proteins measured by SomaScan 7K. A least absolute shrinkage and selection operator (LASSO) regression combined with machine learning approach was employed to develop proteomic predictive models for amyloid PET and tau PET stages. Finally, we compared the model's performance with established CSF Alzheimer's biomarkers (amyloid‐β [Aβ]42, phosphorylated tau [p‐tau]181, and total tau [t‐tau]).ResultWe identified 38 proteins associated with amyloid PET and 128 proteins with tau PET in the amyloid PET‐positive participants. These proteins are primarily related to glucose metabolism and neurotrophic function. Through machine learning, 17 proteins were selected for the panel to differentiate amyloid and tau PET stages. Of these, 9 proteins were specific for distinguishing between amyloid PET‐negative and tau PET‐negative (A‐T‐) and amyloid PET‐positive and tau PET‐positive (A+T‐) (e.g., SMOC1, NEFH), 4 for discriminating A+T‐ and amyloid PET‐positive and tau PET‐positive in the temporal neocortex (A+TNEO+) (e.g., TMOD2, CRNN), with 4 common to both categories (e.g., MMP10, PPIB). We found that a maximum of 8 and a minimum of 2 proteins effectively differentiated A+TNEO+ from A+T‐ (area under curve range: 0.9‐1), and a maximum of 13 and a minimum of 4 proteins discriminated A+T‐ from A‐T‐ (area under curve range: 0.82‐0.92) (Figure 1). The discriminative performance of these protein panels was significantly superior to the established CSF Alzheimer's biomarkers, with or without the addition of risk factors in the models (Figure 2), which we validated using autopsy data.ConclusionIn conclusion, assessing a limited set of proteins can accurately determine distinct pathological stages of Alzheimer's disease, addressing the limitations of current fluid biomarkers in identifying specific disease stages.
Auranofin Alleviates Cognitive Deficit Induced by Cladribine in Experimental Rats
Authors: Aran Khadga Raj 
Published: January 2025

AbstractBackgroundA purine nucleoside called cladribine has been shown to increase toxic amyloid protein and cause impaired cognition. Auranofin is a gold(I)‐containing drug with anti‐inflammatory, antioxidant, anti‐apoptotic, anti‐amyloidogenic, and neuroprotective properties. The goal of the current study was to find out the neuroprotective effects of auranofin against cladribine‐induced Aβ accumulation associated with AD‐like symptoms in experimental rats.Method1 mg/kg, p.o. Cladribine, followed by 5, 10 mg/kg, i.p. auranofin, was given to Wistar rats for 28 days, and behavioral parameters were performed. On day 29, Wistar rats were sacrificed, and the hippocampus part of the brain was isolated for estimation of pro‐neuroinflammatory markers, biochemicals, neurotransmitters, and molecular pathways analysis.ResultRats administrated with cladribine showed elevated cytokine release, oxidative stress, biochemical changes, and a dysbalanced concentration of neurotransmitters. However, auranofin treatment dose‐dependently increased concentrations of antioxidant enzymes decreased the release of proinflammatory cytokines and neurotransmitters and enhanced recognition and spatial memory in rats. Auranofin downregulated tau phosphorylation, Aβ (1–42) levels and regeneration of hippocampal cells. Moreover, the auranofin restoration of the neuroprotective mechanism includes anti‐inflammatory, antioxidant, anti‐apoptotic, anti‐amyloidogenic, and neurotransmitter restoration. Auranofin treatment improved spatial and recognition memory in Wistar rats, restored concentrations of neurotransmitters, antioxidant enzymes and slowed down the release of proinflammatory cytokines in a dose‐dependently way. Additionally, auranofin cleared the accumulation level of Aβ (1–42) and enhanced the Na+/K+‐ATPase activity in the hippocampal cells. Additionally, the histopathological results showed that auranofin mitigates the neuronal death caused by cladribine in the hippocampus.ConclusionWe can conclude that auranofin reduced amyloid‐β (1–42), tau phosphorylation levels, and neurotransmitter balance and improved Na+/K+‐ATPase activity.
Association of Cerebrospinal Fluid BACE1 with Amyloid pathology and Neurodegeneration in Alzheimer disease
Authors: Gao Feng , Shen Yong , Zhang Mengguo 
Published: January 2025

AbstractBackgroundThe exact impacts of β‐site APP cleaving enzyme (BACE1) on brain atrophy and cognitive decline in the Alzheimer’s disease (AD) remain not fully understood. This study aimed to investigate the relationship between BACE1 in cerebrospinal fluid (CSF) and amyloid‐β (Aβ) pathology, neurodegeneration and cognitive function.MethodThis study involved 359 participants from original individuals of the China Aging and Neurodegenerative Disorder Initiative (CANDI) cohort, who underwent measurements of AD biomarkers. Among them, 259 individuals underwent baseline structural magnetic resonance imaging (MRI) scans, 101 individuals underwent 18F‐labeled florbetapir (AV45) positron emission tomography (PET) scans and 117 individuals received 18F‐labeled fluorodeoxyglucose (FDG) PET scans. Additionally, 95 participants underwent follow‐up cognitive tests, and 81 participants received follow‐up structural MRI scans.ResultsOut of the 359 participants, 216 (60.17%) were women. The mean [SD] age was 62.18 [8.48] years, and the mean [SD] follow‐up times for MRI and cognitive tests were 1.52 (0.55) years and 1.79 (0.87) years, respectively. CSF BACE1 levels were elevated in patients with mild cognitive impairment caused by AD or AD. CSF BACE1 levels were correlated with soluble Aβ40 (β = 0.469, p < .001) and Aβ42 (β = 0.174, p = .001), but not AV45‐PET signal. Furthermore, CSF BACE1 levels were positively associated with cortical thickness in specific brain regions, including the insula and supramarginal areas. BACE1 was also linked to cortical glucose metabolism in frontal and supramarginal areas after adjusting regional Aβ burden. Additionally, the longitudinal study revealed that elevated BACE1 levels were associated with reduced cortical thinning in specific brain regions and less cognitive decline (β = ‐0.219, p = .05) over time.ConclusionsWhile increased CSF BACE1 is involved in promoting Aβ production, higher levels of BACE1 are associated with better cortical thickness and cognitive function. Maintaining the normal physiological function of BACE1 in the brain is important for cognitive function.
Functional connectivity patterns among clinical variants of progressive supranuclear palsy
Authors: Sintini Irene , Ali Farwa , Stephens Yehkyoung C. , Clark Heather M. , Stierwalt Julie A.G. , Josephs Keith A. , Whitwell Jennifer L. 
Published: January 2025

AbstractBackgroundProgressive supranuclear palsy (PSP) can present with different clinical variants which show distinct, but partially overlapping, patterns of neurodegeneration and tau deposition in a PSP network of regions, including cerebellar dentate, superior cerebellar peduncle, midbrain, thalamus, basal ganglia, and frontal lobe. We sought to determine whether disruptions in functional connectivity within this PSP network measured using resting‐state functional MRI (rs‐fMRI) differed between PSP‐Richardson’s syndrome and the cortical and subcortical variants of PSP.MethodStructural MRI and rs‐fMRI scans were collected for 40 PSP‐RS, 24 PSP‐cortical (12 speech and language; 10 corticobasal syndrome; 2 frontal) and 36 PSP‐subcortical (18 parkinsonism; 11 progressive gait freezing; 6 postural instability; 1 oculomotor) participants who met the Movement Disorder Society PSP clinical criteria (Table 1). Ninety‐six participants underwent flortaucipir‐PET scans. MRIs were processed using CONN Toolbox. Functional connectivity between seeds placed throughout the PSP network was compared between each PSP group and 83 healthy controls, and between the PSP groups, covarying for age and sex.ResultsConnectivity was reduced throughout the network in PSP‐RS compared to controls (Figure 1A), involving cerebellar dentate, midbrain nuclei, subthalamic nuclei, basal ganglia, thalamus, and frontal regions. Frontal regions showed reduced connectivity to other regions in the network in PSP‐cortical, including substantia nigra and superior cerebellar peduncle. Disruptions in connectivity in PSP‐subcortical were less pronounced, with the strongest disruption between the pallidum and putamen. When PSP groups were compared to each other (Figure 1B), PSP‐RS had lower connectivity from the thalamus and cerebellar dentate to the cortex compared to PSP‐subcortical and from the thalamus to substantia nigra than PSP‐cortical. PSP‐subcortical had lower connectivity from the subthalamic nucleus to caudate than PSP‐RS and from the subthalamic nucleus to substantia nigra than PSP‐cortical and higher connectivity from the thalamus to the prefrontal cortex than both the other variants. Voxel‐based analyses replicated these patterns. There was moderate evidence that tau uptake in the PSP network regions influenced connectivity between these regions in PSP.ConclusionsPatterns of disrupted functional connectivity revealed both variant‐specific and shared disease pathways among PSP variants, providing insight into the disease heterogeneity beyond patterns of atrophy.
Multi‐omic blood biomarkers and cognitive profiles discriminate causes of younger‐onset neurocognitive symptoms: a cohort study
Authors: Bhalala Oneil G , Beamish Jessica , Summerell Patrick , Porter Tenielle , Laws Simon M , Kang Matthew , Huq Aamira , Eratne Dhamidhu , Walterfang Mark , Farrand Sarah , Evans Andrew H , Kelso Wendy , Watson Rosie , Yassi Nawaf , Velakoulis Dennis , Loi Samantha M 
Published: January 2025

AbstractBackgroundYounger‐onset neurocognitive symptoms result from a heterogenous group of neurological and psychiatric disorders which present a diagnostic challenge. To identify such factors, we analysed the BeYOND (Biomarkers in Younger‐Onset Neurocognitive Disorders) cohort, a study of individuals less than 65 years old presenting with neurocognitive symptoms for a clinical diagnosis and who have undergone cognitive and biomarker analyses.Method65 participants were recruited during their index presentation to the Royal Melbourne Hospital Neuropsychiatry Centre, a tertiary specialist service in Melbourne, Australia. Specific diagnoses were clinically determined and categorised as either early‐onset Alzheimer’s disease (AD, n=18), non‐AD neurodegeneration (nAD‐ND, n=23) or primary psychiatric disorders (PPD, n=24). Using Simoa technology, blood levels of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), phosphorylated‐tau at threonine 181 (p‐tau181), amyloid‐β1‐40 (Aβ40), Aβ42 and Aβ42/40 ratio were measured. Apolipoprotein E (APOE) genotypes and polygenic risk scores (PRSs), based on genome‐wide association studies for late‐onset AD, were determined. Generalized linear and multinomial models, as well as information‐theoretic model selection, were used to identify discriminatory factors, adjusted for age and sex.ResultNfL, GFAP and p‐tau181 levels were up to 3‐fold higher in individuals with AD compared to nAD‐ND and PPD (Dunn‐adjusted p<0.05). Aβ‐species levels were not significantly different between the groups. While the PRS was not associated with diagnostic categories (p=0.25), a higher PRS was associated with increased NfL and GFAP levels (OR=1.08, p<0.05). Multi‐omic model selection identified various combinations of NfL and p‐tau181 levels, APOE genotype and global cognitive function as parsimonious models that discriminated between AD and PPD with AUC≥0.975 (95% CI: 0.925–1.000). A model containing only p‐tau181 significantly discriminated between AD and nAD‐ND causes (AUC=0.950, 95% CI: 0.877–1.000). Multinomial regression models identified NfL, GFAP and p‐tau181 as significant variables for discriminating between the three diagnostic categories (p<0.0005).ConclusionDiscriminating between AD, nAD‐ND and PPD causes of younger‐onset neurocognitive symptoms is possible using a combination of cognitive profiling with protein and genetic biomarkers. These results support utilising blood biomarkers for work‐up of younger‐onset neurocognitive symptoms as well as highlight the need for the development of a younger‐onset AD‐specific PRS.
Association of serum‐based mitophagy biomarkers and spatial navigation performance in Alzheimer´s disease
Authors: Laczó Martina , Veverova Katerina , Svacova Zuzana , Katonova Alzbeta , Fang Evandro Fei , Hort Jakub , Vyhnalek Martin , Laczó Jan 
Published: January 2025

AbstractBackgroundMitophagy is a process of intracellular protein homeostasis through which cells eliminate senescent and dysfunctional mitochondria. Altered mitophagy contributes to Alzheimer´s disease (AD) pathology and is associated with worse cognitive functions. We evaluated association of levels of mitophagy proteins (ULK1, BNIP3L, PINK1, and TFEB in serum and ULK1 and PINK 1 in cerebrospinal fluid [CSF]) with spatial egocentric (body‐centered) and allocentric (world‐centered) navigation performance, which is typically impaired in early stages of AD.MethodParticipants with AD aMCI (n=39), mild AD dementia (n=19), and cognitively normal (CN) older adults (n=20) underwent cognitive assessment and brain MRI. Diagnosis of AD was supported by positivity of AD biomarkers in CSF or amyloid PET imaging. Spatial navigation assessment was performed using real‐space and computerized versions of a human analog of the Morris Water Mate Test (hMWM). The hMWM had four tasks: first, with start position and landmarks (combined allocentric‐egocentric), second, only with start position (egocentric), third, only with landmarks (allocentric), and fourth, with landmarks after 30 minutes (allocentric delayed).ResultLevels of mitophagy proteins in the CN group were not associated with performance in any of the spatial navigation tasks (ps > .091). In the AD aMCI group, higher levels of CSF PINK1 were associated with more accurate spatial navigation performance in the computerized egocentric‐allocentric task (r = ‐0.39; p = .030) and the association of higher levels of CSF ULK1 with worse spatial navigation performance in computerized allocentric delayed task approached statistical significance (r = 0.36; p = .054). Levels of mitophagy proteins in the AD dementia group were not associated with performance in any of the spatial navigation tasks (ps > .068).ConclusionHigher level of CSF PINK1 was associated with more accurate egocentric‐allocentric spatial navigation performance in computerized task and higher levels of CSF ULK were associated with worse allocentric navigation performance. These findings support the hypothesis that normal cognition requires efficient mitophagy and more research is needed to evaluate the role of various mitophagy markers in AD.
Correlations between white matter microintegrity and risk level of allostatic load in cognitive complaint subjects
Authors: Contreras Patricio Riquelme , Henriquez Fernando , Godoy Claudio Román , Buller‐Peralta Ingrid , Campo Cecilia Gonzalez , Thumala Daniela , Lillo Patricia , Okuma Cecilia , Demanet Michele , Damm María Francisca , Alvez Pamela Guevara , Wael El‐Deredy , Muniz‐Terrera Graciela , Chonchol Andrea Slachevsky 
Published: January 2025

AbstractBackgroundChronic exposition to stressor factors has been postulated as a cause of structural changes in the brain in the context of dementia. One of these changes can be the fiber integrity loss, that can be measured by diffusion tensor imaging (DTI). We obtained DTI whole brain metrics to relate them with allostatic load in subjects of a chilean cohort of cognitive complaint subjects.MethodWe selected 135 subjects of a chilean cohort of cognitive complaint subjects and classified based in MoCA test in subjects with (58) (MCI) and without (77) (SCC) cognitive decline groups. To measure AL, we selected 15 metabolic, cardiovascular and immunitary biomarkers and the subjects were categorized in low, medium, and high‐risk categories of AL. DTI was calculated using a deterministic tractography algorithm and the relationships were established using a correlational tractoghraphy tool, based in DSIstudio, calculating the FDR (≤ 0,05) of whole brain fasciculus. Age and education was regressed out. After that, fasciculus with significance were segmented based on HCP 1065 atlas.Resultwe obtained significative correlations in many fibers, depending on the parameter studied. Is interesting to note that bilateral cingulum bundles, and corpus callosum integrity are within the fibers that have relationship with allostatic load in both cognitive groups. Additionally, MCI group presents more compromised tracts than SCC group.ConclusionIn this study, a relationship between allostatic load and DTI integrity measurements in MCI and SCC groups was found. An interesting correlation exists in fornix and bilateral cingulum bundles, that can be supported by findings in previous studies based in human and animal models where the stress effects in white matter were studied. These results open an interesting research area to explore the role of stress response and mediators in early steps of dementia, who until today, has been poorly studied.
Adapting the Care Partner Hospital Assessment Tool for Dementia Care
Authors: Fields Beth 
Published: January 2025

AbstractBackgroundCare partners commonly support patients living with dementia (PLWD) during and post‐hospitalization, however, they frequently report feeling excluded from care and unprepared for their caregiving tasks. While the evidence‐informed and validated Care Partner Hospital Assessment Tool (CHAT) was designed to better include and prepare family members and friends, it has not yet been adapted for the growing number of care partners supporting PLWD.ObjectiveTo adapt and finalize the CHAT for care partners of hospitalized PLWD.SettingHospitals in the United States.Study PopulationWe selected hospital‐based clinicians who had at least 5 years of professional experience working with PLWD and their family/friends, and care partners who were at least 18 years old and provided support to a PLWD who experienced a hospitalization. A total of 7 clinicians and 5 care partners were recruited. Clinicians were White (100%), female (85%), and represented social work, nursing, occupational therapy, medicine, and pharmacy. Care partners ranged in age from 41 to 73 years, were White (100%), female (100%), and provided support to a mother or mother‐in‐law (30%), spouse/partner (20%), and other relative (50%).MethodsTwo design teams each consisting of clinicians and care partners respectively—were formed to suggest adaptations to CHAT and share satisfaction with the final tool. Teams completed 5 co‐design videoconference sessions, with 2‐3 weeks between each session. Sessions lasted approximately 60 minutes and were audio recorded. The Rapid Identification of Themes from Audio‐recordings method was used to identify suggestions for adaptation between sessions, and thematic analysis was used to code the transcripts in NVivo.ResultsAdaptations to the CHAT included (a) providing options for dementia specific educational resources, (b) identifying power of attorney and care partner roles and responsibilities (c) using more comprehensive response options and simple language. After making adaptations, participants (100%) reported that they were satisfied or very satisfied with the final Dementia CHAT (i.e., D‐CHAT). Participants described the D‐CHAT as ‘empowering’, ‘comprehensive’, ‘collaborative’, and ‘helpful’.ConclusionThe converged‐upon D‐CHAT is ready for feasibility testing in the hospital setting and may help guide clinicians’ inclusion and preparation of care partners of PLWD.
Formal and informal care use before, during, and after detection of cognitive disorders: a population‐based longitudinal study
Authors: Sakakibara Sakura , Dove Abigail , Guo Jie , Grande Giulia , Sjölund Britt‐Marie , Agerholm Janne , Fratiglioni Laura , Xu Weili 
Published: January 2025

AbstractBackgroundDementia is strongly linked to increased care use, but the use of formal and informal care throughout dementia journey remains unclear.MethodWithin a population‐based cohort study, we identified 240 older adults (aged ≥78 years) with who developed CIND and 155 with incident dementia. These participants were matched to 480 and 310 cognitively intact participants, respectively, and their formal and informal care use and care hours were compared with a control groups before and after diagnosis of cognitive disorders.ResultCompared to cognitively intact participants, those with CIND were more likely to use formal care at the detection (odds ratio [OR] 2.06, 95% confidence interval [95%CI] 1.19‐3.58). Compared to cognitively intact participants, those with dementia were more likely to use formal care before (OR 2.55, 95% CI 1.21‐5.39) and at the wave of (OR 4.38, 95% CI 1.99‐9.65) diagnosis, while informal care use was greater at the wave of (OR 3.75, 95% CI 2.01‐6.99) and after diagnosis (OR 5.05, 95% CI 1.00‐25.64). In linear regression analysis, CIND and dementia were related to a faster increase in informal care hours (β: 5.52, 95% CI 2.87, 8.17/ β: 30.26, 95% CI 24.40, 36.12) compared to controls. Among individuals with CIND/dementia, older age, female sex, secondary educational attainment, and impairments in activities of daily living (ADL) at baseline were significantly associated with formal/informal care use.ConclusionCompared to cognitively intact individuals, those with CIND were associated with increased formal care use at detection, while people with dementia were associated with increased use of formal care already before diagnosis and informal care from diagnosis. CIND and dementia are associated with increased informal care hours. Age, sex, education, and ADL may predict greater care use among people with CIND/dementia.