Microglial VPS35 deficiency impairs Aβ phagocytosis and Aβ-induced disease-associated microglia, and enhances Aβ associated pathology.

ABSTRACT:

Background

Vacuolar sorting protein 35 (VPS35), a key component of the retromer, plays an essential role in selectively retrieval of transmembrane proteins from endosomes to trans-Golgi networks. Dysfunctional retromer is a risk factor for neurodegenerative disorders, including Alzheimer's disease (AD). Microglial VPS35 deficiency is found in AD patients' brain; however, it remains unclear if and how microglial VPS35-loss contributes to AD development.

Methods

We used mice with VPS35 cKO (conditional knockout) in microglial cells in 5XFAD, an AD mouse model. The AD related brain pathology (Aβ and glial activation), behavior, and phagocytosis of Aβ were accessed by a combination of immunofluorescence staining analyses and neurological behavior tests.

Results

A decrease

SUBMITTER: Ren X 

PROVIDER: S-EPMC8892702 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature