Exploring the Genetic Association of the ABAT Gene with Alzheimer's Disease.

Abstract:

:Accumulating evidence demonstrated that GABAergic dysfunction contributes to the pathogenesis of Alzheimer's disease (AD). The GABA aminotransferase (ABAT) gene encodes a mitochondrial GABA transaminase and plays key roles in the biogenesis and metabolism of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter. In this study, we performed an integrative study at the genetic and expression levels to investigate the potential genetic association between the ABAT gene and AD. Through re-analyzing data from the currently largest meta-analysis of AD genome-wide association study (GWAS), we identified genetic variants in the 3'-UTR of ABAT as the top AD-associated SNPs (P < 1 × 10-4) in this gene. Functional annotation of these AD-associated SNPs indicated that these SNPs are located in the regulatory regions of transcription factors or/and microRNAs. Expression quantitative trait loci (eQTL) analysis and luciferase reporter assay showed that the AD risk alleles of these SNPs were associated with a reduced expression level of ABAT. Further analysis of mRNA expression data and single-cell transcriptome data of AD patients showed that ABAT reduction in the neuron is an early event during AD development. Overall, our results indicated that ABAT genetic variants may be associated with AD through affecting its mRNA expression. An abnormal level of ABAT will lead to a disturbance of the GABAergic signal pathway in AD brains.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

Zheng Q,Bi R,Xu M,Zhang DF,Tan LW,Lu YP,Yao YG

doi

10.1007/s12035-020-02271-z

subject

Has Abstract

pub_date

2021-01-06 00:00:00

eissn

0893-7648

issn

1559-1182

pii

10.1007/s12035-020-02271-z

pub_type

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