Gene therapy for Alzheimer's disease targeting CD33 reduces amyloid beta accumulation and neuroinflammation.

ABSTRACT: Neuroinflammation is a key contributor to the pathology of Alzheimer's disease (AD). CD33 (Siglec-3) is a transmembrane sialic acid-binding receptor on the surface of microglial cells. CD33 is upregulated on microglial cells from post-mortem AD patient brains, and high levels of CD33 inhibit uptake and clearance of amyloid beta (Aβ) in microglial cell cultures. Furthermore, knockout of CD33 reduces amyloid plaque burden in mouse models of AD. Here, we tested whether a gene therapy strategy to reduce CD33 on microglia in AD could decrease Aβ plaque load. Intracerebroventricular injection of an adeno-associated virus (AAV) vector-based system encoding an artificial microRNA targeting CD33 (miRCD33) into APP/PS1 mice reduced CD33 mRNA and TBS-soluble Aβ40 and Aβ42 levels in brain extracts. Tr

SUBMITTER: Griciuc A 

PROVIDER: S-EPMC7566501 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature