Deletion of miR-33, a regulator of the ABCA1-APOE pathway, ameliorates neuropathological phenotypes in APP/PS1 mice.

ABSTRACT:

Introduction

Rare variants in ABCA1 increase the risk of developing Alzheimer's disease (AD). ABCA1 facilitates the lipidation of apolipoprotein E (apoE). This study investigated whether microRNA-33 (miR-33)-mediated regulation of this ABCA1-APOE pathway affects phenotypes of an amyloid mouse model.

Methods

We generated mir-33^+/+;APP/PS1 and mir-33^-/-;APP/PS1 mice to determine changes in amyloid pathology using biochemical and histological analyses. We used RNA sequencing and mass spectrometry to identify the transcriptomic and proteomic changes between our genotypes. We also performed mechanistic experiments by determining the role of miR-33 in microglial migration and amyloid beta (Aβ) phagocytosis.

Results

Mir-33 deletion increases ABCA1 level

SUBMITTER: Tate M 

PROVIDER: S-EPMC11567857 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature