Dataset Information

Apolipoprotein E moderates the association between Non-APOE Polygenic Risk Score for Alzheimer's Disease and Aging on Preclinical Cognitive Function.

ABSTRACT:

Introduction

Variation in preclinical cognitive decline suggests additional genetic factors related to Alzheimer's disease (e.g., a non-APOE polygenic risk scores [PRS]) may interact with the APOE ε4 allele to influence cognitive decline.

Methods

We tested the PRS×APOE ε4×age interaction on preclinical cognition using longitudinal data from the Wisconsin Registry for Alzheimer's Prevention. All analyses were fitted using a linear mixed-effects model and adjusted for within individual/family correlation among 1,190 individuals.

Results

We found statistically significant PRS×APOE ε4×age interactions on immediate learning (P=0.038), delayed recall (P<0.001), and Preclinical Alzheimer's Cognitive Composite 3 score (P=0.026). PRS-related differences in overall and memory-related cognitive domains between people with and without APOE ε4 emerge around age 70, with a much stronger adverse PRS effect among APOE ε4 carriers. The findings were replicated in a population-based cohort.

Discussion

APOE ε4 can modify the association between PRS and cognition decline.

SUBMITTER: Xu Y

PROVIDER: S-EPMC10312823 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

Apolipoprotein E moderates the association between Non-<i>APOE</i> Polygenic Risk Score for Alzheimer's Disease and Aging on Preclinical Cognitive Function.

Xu Yuexuan Y Sun Zhongxuan Z Jonaitis Erin E Deming Yuetiva Y Lu Qiongshi Q Johnson Sterling C SC Engelman Corinne D CD

medRxiv : the preprint server for health sciences 20230612

<h4>Introduction</h4>Variation in preclinical cognitive decline suggests additional genetic factors related to Alzheimer's disease (e.g., a non-<i>APOE</i> polygenic risk scores [PRS]) may interact with the <i>APOE</i> ε4 allele to influence cognitive decline.<h4>Methods</h4>We tested the PRS×<i>APOE</i> ε4×age interaction on preclinical cognition using longitudinal data from the Wisconsin Registry for Alzheimer's Prevention. All analyses were fitted using a linear mixed-effects model and adjust ...[more]

PMID: 37398140

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