Inhibition of IFITM3 in cerebrovascular endothelium alleviates Alzheimer's-related phenotypes.

ABSTRACT:

Introduction

Interferon-induced transmembrane protein 3 (IFITM3) modulates γ-secretase in Alzheimer's Disease (AD). Although IFITM3 knockout reduces amyloid β protein (Aβ) production, its cell-specific effect on AD remains unclear.

Methods

Single nucleus RNA sequencing (snRNA-seq) was used to assess IFITM3 expression. Adeno-associated virus-BI30 (AAV-BI30) was injected to reduce IFITM3 expression in the cerebrovascular endothelial cells (CVECs). The effects on AD phenotypes in cells and AD mice were examined through behavioral tests, two-photon imaging, flow cytometry, Western blot, immunohistochemistry, and quantitative polymerase chain reaction assay (qPCR).

Results

IFITM3 expression was increased in the CVECs of patients with AD. Overexpression of IFITM3 in primary

SUBMITTER: Feng Y 

PROVIDER: S-EPMC11851164 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature