Genetic risk score for Alzheimer's disease predicts brain volume differences in mid and late life in UK biobank participants.

ABSTRACT:

Introduction

We estimated the ages when associations between Alzheimer's disease (AD) genes and brain volumes begin among middle-aged and older adults.

Methods

Among 45,616 dementia-free participants aged 45-80, linear regressions tested whether genetic risk score for AD (AD-GRS) had age-dependent associations with 38 regional brain magnetic resonance imaging volumes. Models were adjusted for sex, assessment center, genetic ancestry, and intracranial volume.

Results

AD-GRS modified the estimated effect of age (per decade) on the amygdala (-0.41 mm³ [-0.42, -0.40]); hippocampus (-0.45 mm³ [-0.45, -0.44]), nucleus accumbens (-0.55 mm³ [-0.56, -0.54]), thalamus (-0.38 mm³ [-0.39, -0.37]), and medial orbitofrontal cortex (-0.23 mm³ [-0.24, -0.22]). Trends began by age 45 for the nucleus accumbens and thalamus, 48 for the hippocampus, 51 for the amygdala, and 53 for the medial orbitofrontal cortex. An AD-GRS excluding apolipoprotein E (APOE) was additionally associated with entorhinal and middle temporal cortices.

Discussion

APOE and other genes that increase AD risk predict lower hippocampal and other brain volumes by middle age.

SUBMITTER: Buto PT 

PROVIDER: S-EPMC10984491 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature