Introduction: Multi-omics studies in Alzheimer's disease (AD) revealed many potential disease pathways and therapeutic targets. Despite their promise of precision medicine, these studies lacked Black Americans (BA) and Latin Americans (LA), who are disproportionately affected by AD.
Methods: To bridge this gap, Accelerating Medicines Partnership in Alzheimer's Disease (AMP-AD) expanded brain multi-omics profiling to multi-ethnic donors.
Results: We generated multi-omics data and curated and harmonized phenotypic data from BA (n = 306), LA (n = 326), or BA and LA (n = 4) brain donors plus non-Hispanic White (n = 252) and other (n = 20) ethnic groups, to establish a foundational dataset enriched for BA and LA participants. This study describes the data available to the research community, including transcriptome from three brain regions, whole genome sequence, and proteome measures.
Discussion: The inclusion of traditionally underrepresented groups in multi-omics studies is essential to discovering the full spectrum of precision medicine targets that will be pertinent to all populations affected with AD.
Highlights: Accelerating Medicines Partnership in Alzheimer's Disease Diversity Initiative led brain tissue profiling in multi-ethnic populations. Brain multi-omics data is generated from Black American, Latin American, and non-Hispanic White donors. RNA, whole genome sequencing and tandem mass tag proteomicsis completed and shared. Multiple brain regions including caudate, temporal and dorsolateral prefrontal cortex were profiled.
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http://dx.doi.org/10.1002/alz.14208 | DOI Listing |
Sci Rep
December 2024
Department of Medical Microbiology, Radboudumc, Nijmegen, The Netherlands.
The aetiology of Alzheimer's disease (AD) and Parkinson's disease (PD) are unknown and tend to manifest at a late stage in life; even though these neurodegenerative diseases are caused by different affected proteins, they are both characterized by neuroinflammation. Links between bacterial and viral infection and AD/PD has been suggested in several studies, however, few have attempted to establish a link between fungal infection and AD/PD. In this study we adopted a nanopore-based sequencing approach to characterise the presence or absence of fungal genera in both human brain tissue and cerebrospinal fluid (CSF).
View Article and Find Full Text PDFNat Commun
December 2024
Department of Theory and Bio-Systems, Max Planck Institute of Colloids and Interfaces, 14476, Potsdam, Germany.
Neurodegeneration in Huntington's disease (HD) is accompanied by the aggregation of fragments of the mutant huntingtin protein, a biomarker of disease progression. A particular pathogenic role has been attributed to the aggregation-prone huntingtin exon 1 (HTTex1), generated by aberrant splicing or proteolysis, and containing the expanded polyglutamine (polyQ) segment. Unlike amyloid fibrils from Parkinson's and Alzheimer's diseases, the atomic-level structure of HTTex1 fibrils has remained unknown, limiting diagnostic and treatment efforts.
View Article and Find Full Text PDFNat Commun
December 2024
Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
Impaired muscle mitochondrial oxidative capacity is associated with future cognitive impairment, and higher levels of PET and blood biomarkers of Alzheimer's disease and neurodegeneration. Here, we examine its associations with up to over a decade-long changes in brain atrophy and microstructure. Higher in vivo skeletal muscle oxidative capacity via MR spectroscopy (post-exercise recovery rate, k) is associated with less ventricular enlargement and brain aging progression, and less atrophy in specific regions, notably primary sensorimotor cortex, temporal white and gray matter, thalamus, occipital areas, cingulate cortex, and cerebellum white matter.
View Article and Find Full Text PDFJ Neuroimaging
December 2024
Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
Background And Purpose: In idiopathic normal pressure hydrocephalus (iNPH) patients, cerebrospinal fluid (CSF) flow is typically evaluated with a cardiac-gated two-dimensional (2D) phase-contrast (PC) MRI through the cerebral aqueduct. This approach is limited by the evaluation of a single location and does not account for respiration effects on flow. In this study, we quantified the cardiac and respiratory contributions to CSF movement at multiple intracranial locations using a real-time 2D PC-MRI and evaluated the diagnostic value of CSF dynamics biomarkers in classifying iNPH patients.
View Article and Find Full Text PDFBackground: Atrial fibrillation (AF) is associated with cognitive decline. Use of oral anticoagulant (OAC) medications offers a lower risk of dementia, but it is unclear whether differences exist between types of OAC agents.
Objective: This was a secondary analysis to explore whether the progression from normal cognition to mild cognitive impairment to dementia differs between adults with AF on warfarin versus non-vitamin K inhibitors medications (NOACs) using data extracted from the National Alzheimer's Coordinating Center clinical case series.
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