Year: 2026
Type: article
Study design: Observational Study
Abstract: INTRODUCTION: Lifestyle and environmental factors contributing to cardiovascular risk are components of the exposome, yet molecular signatures associated with cumulative cardiovascular risk in Alzheimer's disease (AD) remain incompletely understood. METHODS: We analyzed blood-based transcriptomics data from two independent cohorts: Seoul National University Bundang Hospital (SNUBH; N = 148, Korean) and Alzheimer's Disease Neuroimaging Initiative (ADNI; N = 743, predominantly European ancestry). Framingham cardiovascular risk score (FRS)-associated co-expression network modules were identified, followed by pathway-based enrichment, hub gene-based participant stratification, and bidirectional cross-cohort discovery-replication analyses. RESULTS: Two co-expression modules were associated with FRS in SNUBH, and six in ADNI. Bidirectional analyses identified two preserved modules with consistent module-FRS associations across cohorts, enriched in pathways implicated in cellular responses to exposure, including RNA-protein homeostasis, mitochondrial function, and hematopoietic processes. Hub genes in the two modules stratified participants into molecularly distinct subgroups concordant with clinical FRS categories. DISCUSSION: FRS-associated molecular pathways were identified and warrant further investigation as potential targets for risk modification.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.71930
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,200
Funders: U.S. Department of Defense, Alzheimer's Association, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Biogen, University of Southern California, F. Hoffmann-La Roche, Meso Scale Diagnostics, Alzheimer's Disease Neuroimaging Initiative, BioClinica, Novartis Pharmaceuticals Corporation, Northern California Institute for Research and Education, National Research Foundation of Korea, Eisai, Servier, H. Lundbeck A/S, Ministry of Science and ICT, South Korea, IXICO, National Institutes of Health, Genentech, Canadian Institutes of Health Research, National Institute on Aging
Awards: G1012222616, G1298807586, G1554142629, G1593117279, G1594299860, G1650819308, G1876162387, G1880935189, G2100670906, G2152643862, G2189010064, G2340207221, G2423387114, G2471646051, G2522063444, G2835601961, G29951154, G3131374986, G3216574877, G3285524069, G3553156159, G3710456697, G3752451908, G3870774570, G3908963977, G3966393351, G43180419, G4501223628, G4800177743, G5207404921, G5209990037, G528601746, G5365730499, G5654639750, G5740349702, G613619302, G6173816828, G6210868510, G6328151403, G6371410416, G6412110892, G6447063303, G6719828067, G6792506723, G6899163935, G6948409098, G72415811, G7298697282, G764699806, G7799614282, G781725486, G8228018387, G8281378126, G839208290, G8405789483, G8662522981, G8852128998, G8895907669, G8897063270, G8957659042, G9000039018, G9000120983, G9000122335, Indiana Alzheimer's Disease Research Center, Centrally-linked longitudinal peripheral biomarkers of AD in multi-ethnic populations
OpenAlex ID: W7223558303