Alzheimer's disease-associated CD33 is expressed by inflammatory monocytes and is not significantly expressed in the brain

Abstract summary

Showed that CD33 (Siglec-3) expression in human microglia impairs amyloid-beta uptake and clearance. The Alzheimer's risk-associated CD33 variant rs3865444 reduces CD33 expression and increases microglial amyloid clearance. CD33 knockout mice show enhanced microglial amyloid phagocytosis and reduced plaque burden.

Evidence labels

Therapeutic relevance

Established CD33 as an inhibitory receptor that limits microglial clearance function; CD33 blocking antibodies in development.