Non-APOE variants predominately expressed in smooth muscle cells contribute to the influence of Alzheimer's disease genetic risk on white matter hyperintensities.

ABSTRACT:

Introduction

White matter hyperintensity volumes (WMHVs) are disproportionally prevalent in individuals with Alzheimer's disease (AD), potentially reflecting neurovascular injury. We quantify the association between AD polygenic risk score (AD-PRS) and WMHV, exploring single-nucleotide polymorphisms (SNPs) that are proximal to genes overexpressed in cerebrovascular cell species.

Methods

In a UK-Biobank sub-sample (mean age = 64, range = 45-81 years), we associate WMHV with (1) AD-PRS estimated via SNPs across the genome (minus apolipoprotein E [APOE] locus) and (2) AD-PRS estimated with SNPs proximal to specific genes that are overexpressed in cerebrovascular cell species.

Results

We observed a positive association between non-APOE-AD-PRS and WMHVs. We further demonst

SUBMITTER: Chandler HL 

PROVIDER: S-EPMC11848156 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature