Identification of methylation-regulated genes modulating microglial phagocytosis in hyperhomocysteinemia-exacerbated Alzheimer's disease.

ABSTRACT:

Background

Hyperhomocysteinemia (HHcy) has been linked to development of Alzheimer's disease (AD) neuropathologically characterized by the accumulation of amyloid β (Aβ). Microglia (MG) play a crucial role in uptake of Aβ fibrils, and its dysfunction worsens AD. However, the effect of HHcy on MG Aβ phagocytosis remains unstudied.

Methods

We isolated MG from the cerebrum of HHcy mice with genetic cystathionine-β-synthase deficiency (Cbs^-/-) and performed bulk RNA-seq. We performed meta-analysis over transcriptomes of Cbs^-/- mouse MG, human and mouse AD MG, MG Aβ phagocytosis model, human AD methylome, and GWAS AD genes.

Results

HHcy and hypomethylation conditions were identified in Cbs^-/- mice. Through Cbs^-/- MG transcriptome

SUBMITTER: Wang X 

PROVIDER: S-EPMC10546779 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature