Increased APOE ε4 expression is associated with the difference in Alzheimer's disease risk from diverse ancestral backgrounds.
Alzheimers Dement
; 17(7): 1179-1188, 2021 07.
Article
em En
| MEDLINE
| ID: mdl-33522086
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 (chr1944-46Mb), 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, with high APOE ε4 expression and specific to ELA, is suggestive of A1 reactive astrocytes.DISCUSSION:
AD patients with ELA expressed significantly greater levels of APOE than ALA APOE ε4 carriers. These differences in APOE expression could contribute to the reduced risk for AD seen in African APOE ε4 carriers.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Análise de Sequência de RNA
/
População Negra
/
População Branca
/
Apolipoproteína E4
/
Doença de Alzheimer
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Aged
/
Aged80
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article