Astrocyte-derived clusterin suppresses amyloid formation in vivo.

ABSTRACT:

Background

Accumulation of amyloid-β (Aβ) peptide in the brain is a pathological hallmark of Alzheimer's disease (AD). The clusterin (CLU) gene confers a risk for AD and CLU is highly upregulated in AD patients, with the common non-coding, protective CLU variants associated with increased expression. Although there is strong evidence implicating CLU in amyloid metabolism, the exact mechanism underlying the CLU involvement in AD is not fully understood or whether physiologic alterations of CLU levels in the brain would be protective.

Results

We used a gene delivery approach to overexpress CLU in astrocytes, the major source of CLU expression in the brain. We found that CLU overexpression resulted in a significant reduction of total and fibrillar amyloid in both cortex and hip

SUBMITTER: Wojtas AM 

PROVIDER: S-EPMC7694353 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature