Scara1 deficiency impairs clearance of soluble amyloid-? by mononuclear phagocytes and accelerates Alzheimer's-like disease progression.

ABSTRACT: In Alzheimer's disease, soluble amyloid-? causes synaptic dysfunction and neuronal loss. Receptors involved in clearance of soluble amyloid-? are not known. Here we use short hairpin RNA screening and identify the scavenger receptor Scara1 as a receptor for soluble amyloid-? expressed on myeloid cells. To determine the role of Scara1 in clearance of soluble amyloid-? in vivo, we cross Scara1 null mice with PS1-APP mice, a mouse model of Alzheimer's disease, and generate PS1-APP-Scara1-deficient mice. Scara1 deficiency markedly accelerates A? accumulation, leading to increased mortality. In contrast, pharmacological upregulation of Scara1 expression on mononuclear phagocytes increases A? clearance. This approach is a potential treatment strategy for Alzheimer's disease.

SUBMITTER: Frenkel D 

PROVIDER: S-EPMC3702268 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature