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Associations of APOE-TOMM40-APOC1 Variants With Alzheimer’s Disease Biomarkers | Aging-US

Aging-US published this research paper as the cover for Volume 14, Issue 24, entitled, "Associations of the APOE ε2 and ε4 alleles and polygenic profiles comprising APOE-TOMM40-APOC1 variants with Alzheimer’s disease biomarkers" by researchers from Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Durham, NC; Center for Imaging of Neurodegenerative Disease, University of California, San Francisco, CA. #openaccess #aging #alzheimersdisease #ad #alzheimer #biomarkers #peerreview #openscience #research DOI - https://doi.org/10.18632/aging.204384 Corresponding author - Alexander M. Kulminski - [email protected] Abstract Capturing the genetic architecture of Alzheimer’s disease (AD) is challenging because of the complex interplay of genetic and non-genetic factors in its etiology. It has been suggested that AD biomarkers may improve the characterization of AD pathology and its genetic architecture. Most studies have focused on connections of individual genetic variants with AD biomarkers, whereas the role of combinations of genetic variants is substantially underexplored. We examined the associations of the APOE ε2 and ε4 alleles and polygenic profiles comprising the ε4-encoding rs429358, TOMM40 rs2075650, and APOC1 rs12721046 polymorphisms with cerebrospinal fluid (CSF) and plasma amyloid β (Aβ40 and Aβ42) and tau biomarkers. Our findings support associations of the ε4 alleles with both plasma and CSF Aβ42 and CSF tau, and the ε2 alleles with baseline, but not longitudinal, CSF Aβ42 measurements. We found that the ε4-bearing polygenic profiles conferring higher and lower AD risks are differentially associated with tau but not Aβ42. Modulation of the effect of the ε4 alleles by TOMM40 and APOC1 variants indicates the potential genetic mechanism of differential roles of Aβ and tau in AD pathogenesis. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/e... Keywords - aging, apolipoprotein E polymorphism, Alzheimer’s disease, haplotypes, Alzheimer’s disease biomarkers About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud -   / aging-us   Facebook -   / agingus   Twitter -   / agingjrnl   Instagram -   / agingjrnl   YouTube -    / agingus​   LinkedIn -   / aging   Pinterest -   / agingus   Media Contact 18009220957 [email protected]