Gas6 induces inflammation and reduces plaque burden but worsens behavior in a sex-dependent manner in the APP/PS1 model of Alzheimer's disease.

ABSTRACT:

Background

Alzheimer's disease is the leading cause of dementia worldwide. TAM receptor tyrosine kinases (Tyro3, Axl, MerTK) are known for their role in engagement of phagocytosis and modulation of inflammation, and recent evidence suggests a complex relationship between Axl, Mer, and microglial phagocytosis of amyloid plaques in AD. Gas6, the primary CNS TAM ligand, reduces neuroinflammation and improves outcomes in murine models of CNS disease. Therefore, we hypothesized that AAV-mediated overexpression of Gas6 would alleviate plaque pathology, reduce neuroinflammation, and improve behavior in the APP/PS1 model of Alzheimer's disease.

Methods

Adeno-associated viral vectors were used to overexpress Gas6 in the APP/PS1 model of Alzheimer's disease. Nine-month-old male and fe

SUBMITTER: Owlett LD 

PROVIDER: S-EPMC8822838 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature