Children’s Nutrition Research Center Staff Publications

Language

English

Publication Date

11-1-2025

Journal

Journal of Alzheimer's Disease

DOI

10.1177/13872877251375098

PMID

40924585

PMCID

PMC12541115

PubMedCentral® Posted Date

9-9-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Genetic risk prediction for Alzheimer's disease (AD) has high potential impact, yet few studies have assessed the reliability of various polygenic risk score (PRS) methods at the individual level. Here, we evaluated the reliability of AD PRS estimates among 6338 participants from the Multi-Ethnic Study of Atherosclerosis. We compared four PRS models that have been previously associated with dementia risk. Despite similar population-level performance metrics, inter-model reliability of individual-level risk assessment was low, even among individuals classified in the top and bottom deciles. These findings raise serious concerns about the downstream application of PRS for guiding interventions for AD.

Keywords

Humans, Alzheimer Disease, Male, Female, Multifactorial Inheritance, Aged, Reproducibility of Results, Genetic Predisposition to Disease, Risk Assessment, Aged, 80 and over, Risk Factors, Genetic Risk Score, Alzheimer's disease, polygenic risk score, reliability, translational

Published Open-Access

yes

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