Age-dependent interactions of APOE isoform 4 and Alzheimer’s disease neuropathology: findings from the NACC
Year: 2025
Type: article
Abstract: Alzheimer's disease related pathologies, neurodegenerative pathologies, and vascular neuropathologies are common in older adults at death. Previous studies using the National Alzheimer's Coordinating Center (NACC) have not investigated the association between age at death and apolipoprotein E (APOE) ε4 and the prevalence of neuropathologies found at autopsy. We used autopsy confirmed neuropathology data from the NACC to examine the interactive effects of age and APOE ε4 on various neuropathologies (N = 5,843) using modified Poisson regression to estimate the prevalence ratios. Significant interactions between APOE ε4 and age at death were observed for neuritic plaques, Braak staging, diffuse neuritic plaques, and Lewy body disease pathology, with the effect of APOE ε4 decreasing at older ages. In contrast, a significant positive interaction was found for hemorrhages/microbleeds, indicating that the association between APOE ε4 and microbleeds strengthens with increasing age. These findings suggest that future therapeutic strategies should consider both genetic risk and age to effectively target AD progression.
Institutions: Stanford Medicine, Stanford University, Johns Hopkins University
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,790
Awards: G1024368718, G1048051091, G1069732457, G117713310, G120189231, G1269895679, G1458362881, G1593128567, G1753564228, G1827328465, G1859882300, G2190936067, G2234397790, G2434699210, G2476446273, G253265979, G2622865600, G2675915175, G2742075923, G343469054, G348743638, G3703765782, G3952091757, G415047313, G4186766937, Nevada Exploratory Alzheimer's Disease Research Center (NVEADRC), G4788296895, UAB Alzheimer's Disease Research Center, G504619356, G5640525220, Mitochondrial health, cardiovascular risk, and blood pressure targets in hypertensive adults, New Mexico Alzheimer's Disease Research Center, Cardiovascular and Cerebrovascular Risk Factors for Mobility Limitation in the Jackson Heart Study, Vanderbilt Alzheimer's Disease Research Center, G816726602, Pathways to Neurosciences, Boston University Alzheimer's Disease Research Center, Yale Alzheimer Disease Research Center, UCSD Shiley-Marcos Alzheimer's Disease Research Center P30, Joint Estimate Diffusion Imaging (JEDI) for improved Tissue Characterization and Neural Connectivity in Aging and Alzheimer's Disease, University of Kansas Alzheimer's Disease Research Center (KU ADRC), Alzheimer Disease Research Center, Alzheimer's Disease Research Center, Johns Hopkins Alzheimer's Disease Research Center, Stanford Alzheimer's Disease Research Center, University of Washington Alzheimer's Disease Research Center, Wisconsin Alzheimer's Disease Research Center, Alzheimer's Disease Research Centers, University of Kentucky Alzheimer's Disease Research Center, Penn Alzheimer's Disease Research Center (ADRC), Massachusetts Alzheimer's Disease Research Center (MADRC), Goizueta Alzheimer's Disease Research Center, The Alzheimer's Disease Research Center at the University of California, Irvine, G990712341
OpenAlex ID: W4410464341