Selective reduction of astrocyte apoE3 and apoE4 strongly reduces Aβ accumulation and plaque-related pathology in a mouse model of amyloidosis.

ABSTRACT:

Background

One of the key pathological hallmarks of Alzheimer disease (AD) is the accumulation of the amyloid-β (Aβ) peptide into amyloid plaques. The apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset AD and has been shown to influence the accumulation of Aβ in the brain in an isoform-dependent manner. ApoE can be produced by different cell types in the brain, with astrocytes being the largest producer of apoE, although reactive microglia also express high levels of apoE. While studies have shown that altering apoE levels in the brain can influence the development of Aβ plaque pathology, it is not fully known how apoE produced by specific cell types, such as astrocytes, contributes to amyloid pathology.

Methods

We utilized APOE knock-in mice ca

SUBMITTER: Mahan TE 

PROVIDER: S-EPMC8811969 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature