UC Irvine

Alzheimer’s Disease (AD) is the most prevalent form of dementia and a leading cause of death. Disease hallmarks include chronic neuroinflammation and impaired clearance of toxic protein aggregates. We use exogenous CD200 to polarize microglia towards a state that measurably dampens inflammation and enhances uptake of amyloid-beta fibrils (fAβ42). Electron microscopy revealed the presence of single membrane vesicles in CD200-treated microglia associated with elevated LC3 expression. Together these data suggest CD200 enhances LC3-associated endocytosis (LANDO) which mediates cell surveillance and enables LC3-associated phagocytosis of fAβ42. Finally, we assess the effects of CD200 treatment on mitochondrial health. CD200 treatment protected microglia from Aβ-induced mitochondrial damage despite increased levels of free NADH/NADPH. Together, our data suggests CD200 treatment dampens inflammation, enhances LANDO-mediated cell surveillance and LAP-mediated clearance of Aβ, and protects mitochondria from Aβ-induced damage.