Nomination of a novel plasma protein biomarker panel capable of classifying Alzheimer’s disease dementia with high accuracy in an African American cohort DOI Creative Commons
Lindsey A. Kuchenbecker, Kevin J. Thompson, Cheyenne Hurst

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 29, 2024

Abstract Introduction African Americans (AA) are widely underrepresented in plasma biomarker studies for Alzheimer’s disease (AD) and current diagnostic candidates do not reflect the heterogeneity of AD. Methods Untargeted proteome measurements were obtained using SomaScan 7k platform to identify novel biomarkers AD a cohort AA clinically diagnosed as dementia (n=183) or cognitively unimpaired (CU, n=145). Machine learning approaches implemented set proteins that yields best classification accuracy. Results A protein panel achieved an area under curve (AUC) 0.91 classify vs CU. The reproducibility this finding was observed ANMerge AMP-AD Diversity brain datasets (AUC=0.83; AUC=0.94). Discussion This study demonstrates potential discovery through untargeted proteomics machine approaches. Our findings also highlight importance matrisome cerebrovascular dysfunction pathophysiology.

Язык: Английский

Integrative proteomics identifies a conserved Aβ amyloid responsome, novel plaque proteins, and pathology modifiers in Alzheimer’s disease DOI Creative Commons
Yona Levites, Eric B. Dammer,

Yong Ran

и другие.

Cell Reports Medicine, Год журнала: 2024, Номер 5(8), С. 101669 - 101669

Опубликована: Авг. 1, 2024

Alzheimer's disease (AD) is a complex neurodegenerative disorder that develops over decades. AD brain proteomics reveals vast alterations in protein levels and numerous altered biologic pathways. Here, we compare proteome network changes with the proteomes of amyloid β (Aβ)-depositing mice to identify conserved divergent networks identifying an Aβ responsome. Proteins most (M42) accumulate plaques, cerebrovascular (CAA), and/or dystrophic neuronal processes, overexpression two M42 proteins, midkine (Mdk) pleiotrophin (PTN), increases accumulation plaques CAA. proteins bind fibrils vitro, MDK PTN co-accumulate cardiac transthyretin amyloid. appear intimately linked deposition can regulate deposition, suggesting they are pathology modifiers thus putative therapeutic targets. We posit amyloid-scaffolded M42+ central mechanism mediating downstream pathophysiology AD.

Язык: Английский

Процитировано

12
Large-scale Deep Proteomic Analysis in Alzheimer’s Disease Brain Regions Across Race and Ethnicity DOI Creative Commons
Fatemeh Seifar,

Edward J. Fox,

Anantharaman Shantaraman

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 26, 2024

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet our comprehension predominantly relies on studies within non-Hispanic White (NHW) population. Here we aimed to provide comprehensive insights into proteomic landscape of AD across diverse racial and ethnic groups.

Язык: Английский

Процитировано

6
Bridging the gap: Multi‐omics profiling of brain tissue in Alzheimer's disease and older controls in multi‐ethnic populations DOI Creative Commons
Joseph S. Reddy, Laura Heath, Abby Vander Linden

и другие.

Alzheimer s & Dementia, Год журнала: 2024, Номер 20(10), С. 7174 - 7192

Опубликована: Авг. 30, 2024

Abstract INTRODUCTION Multi‐omics studies in Alzheimer's disease (AD) revealed many potential pathways and therapeutic targets. Despite their promise of precision medicine, these lacked Black Americans (BA) Latin (LA), who are disproportionately affected by AD. METHODS To bridge this gap, Accelerating Medicines Partnership Disease (AMP‐AD) expanded brain multi‐omics profiling to multi‐ethnic donors. RESULTS We generated data curated harmonized phenotypic from BA ( n = 306), LA 326), or 4) donors plus non‐Hispanic White 252) other 20) ethnic groups, establish a foundational dataset enriched for participants. This study describes the available research community, including transcriptome three regions, whole genome sequence, proteome measures. DISCUSSION The inclusion traditionally underrepresented groups is essential discovering full spectrum medicine targets that will be pertinent all populations with Highlights Diversity Initiative led tissue populations. Brain American, RNA, sequencing tandem mass tag proteomicsis completed shared. Multiple regions caudate, temporal dorsolateral prefrontal cortex were profiled.

Язык: Английский

Процитировано

5
Integrative Epigenomic Landscape of Alzheimer's Disease Brains Reveals Oligodendrocyte Molecular Perturbations Associated with Tau DOI Open Access

Stephanie R. Oatman,

Joseph S. Reddy,

Amin Atashgaran

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 17, 2025

Abstract Alzheimer’s disease (AD) brains are characterized by neuropathologic and biochemical changes that highly variable across individuals. Capturing epigenetic factors associate with this variability can reveal novel biological insights into AD pathophysiology. We conducted an epigenome-wide association study of DNA methylation (DNAm) in 472 measures (Braak stage, Thal phase, cerebral amyloid angiopathy score) brain levels five proteins (APOE, amyloid-β (Aβ)40, Aβ42, tau, p-tau) core to pathogenesis. Using a regional (rCpGm) approach, we identified 5,478 significant associations, 99.7% which were tau measures. Of the tau-associated rCpGms, 93 had concordant associations external datasets comprising 1,337 samples. Integrative transcriptome-methylome analyses uncovered 535 gene expression for these rCpGms. Genes concurrent perturbations enriched oligodendrocyte marker genes, including known risk genes such as BIN1 , myelination MYRF, MBP MAG previously implicated AD, well like LDB3 . further annotated top additional 6 single cell 2 bulk transcriptome from two other tauopathies, Pick’s progressive supranuclear palsy (PSP). Our findings support consistent rCpGm tauopathies tau-related phenotypes both tissue clusters. In summary, uncover integrative epigenomic landscape demonstrate common potential pathomechanism different tauopathies.

Язык: Английский

Процитировано

0
Nomination of a novel plasma protein biomarker panel capable of classifying Alzheimer’s disease dementia with high accuracy in an African American cohort DOI Creative Commons
Lindsey A. Kuchenbecker, Kevin J. Thompson, Cheyenne Hurst

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 29, 2024

Abstract Introduction African Americans (AA) are widely underrepresented in plasma biomarker studies for Alzheimer’s disease (AD) and current diagnostic candidates do not reflect the heterogeneity of AD. Methods Untargeted proteome measurements were obtained using SomaScan 7k platform to identify novel biomarkers AD a cohort AA clinically diagnosed as dementia (n=183) or cognitively unimpaired (CU, n=145). Machine learning approaches implemented set proteins that yields best classification accuracy. Results A protein panel achieved an area under curve (AUC) 0.91 classify vs CU. The reproducibility this finding was observed ANMerge AMP-AD Diversity brain datasets (AUC=0.83; AUC=0.94). Discussion This study demonstrates potential discovery through untargeted proteomics machine approaches. Our findings also highlight importance matrisome cerebrovascular dysfunction pathophysiology.

Язык: Английский

Процитировано

1