Exploring potential mechanisms of an African protective locus for Alzheimer's disease in APOEε4 carriers.

ABSTRACT:

Introduction

We recently described that the African-specific A allele of rs10423769, which lies in an area of segmental duplications, reduces Alzheimer's disease (AD) risk by ∼ 75% in apolipoprotein E (APOE) ε4 homozygotes.

Methods

Short and long-read sequencing were used to identify the haplotype harboring rs10423769_A and examine DNA methylation and structural variation (SV).

Results

A unique 21 kb haplotype is shared amongst all rs10423769_A carriers (r² > 0.95) and is present in all African ancestry tested. We identified methylation differences between the non-protective and rs10423769_A haplotypes. An expanded variable number tandem repeat (VNTR) containing multiple MEF2-family transcription factor binding motifs in LD with the protective haplotype. Fu

SUBMITTER: Bertholim-Nasciben L 

PROVIDER: S-EPMC12287753 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature