Association of a Total Cholesterol Polygenic Score with Cholesterol Levels and Pathological Biomarkers across the Alzheimer's Disease Spectrum.

ABSTRACT: Midlife hypercholesterolemia is a well-known risk factor for sporadic Alzheimer's disease (AD), and like AD, it is highly influenced by genetics with heritability estimates of 32-63%. We thus hypothesized that genetics underlying peripheral blood total cholesterol (TC) levels could influence the risk of developing AD. We created a weighted polygenic score (TC-PGS) using summary data from a meta-analysis of TC genome-wide association studies for evaluation in three independent AD-related cohorts spanning pre-clinical, clinical, and pathophysiologically proved AD. APOE-ε4 variant was purposely included in the analysis as it represents an already well-established genetic risk factor for both AD and circulating TC. We could vastly improve the performance of the score when considering p-

SUBMITTER: Nilsson NIV 

PROVIDER: S-EPMC8623969 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature