Increased APOE ε4 expression is associated with the difference in Alzheimer's disease risk from diverse ancestral backgrounds.

ABSTRACT:

Introduction

Apolipoprotein E (APOE) ε4 confers less risk for Alzheimer's disease (AD) in carriers with African local genomic ancestry (ALA) than APOE ε4 carriers with European local ancestry (ELA). Cell type specific transcriptional variation between the two local ancestries (LAs) could contribute to this disease risk differences.

Methods

Single-nucleus RNA sequencing was performed on frozen frontal cortex of homozygous APOE ε4/ε4 AD patients: seven with ELA, four with ALA.

Results

A total of 60,908 nuclei were sequenced. Within the LA region (chr19:44-46Mb), APOE was the gene most differentially expressed, with ELA carriers having significantly more expression (overall P < 1.8E^-317 ) in 24 of 32 cell clusters. The transcriptome of one astrocyte cluster, w

SUBMITTER: Griswold AJ 

PROVIDER: S-EPMC8843031 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature