Scara1 deficiency impairs clearance of soluble amyloid-β by mononuclear phagocytes and accelerates Alzheimer’s-like disease progression

In Alzheimer’s disease, soluble amyloid-β causes synaptic dysfunction and neuronal loss. Receptors involved in clearance of soluble amyloid-β are not known. Here we use short hairpin RNA screening and identify the scavenger receptor Scara1 as a receptor for soluble amyloid-β expressed on myeloid cells. To determine the role of Scara1 in clearance of soluble amyloid-β 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 Aβ accumulation, leading to increased mortality. In contrast, pharmacological upregulation of Scara1 expression on mononuclear phagocytes increases Aβ clearance. This approach is a potential treatment strategy for Alzheimer’s disease. The scavenger receptor Scara1 , expressed on microglia and macrophages, binds beta amyloid aggregates. In a mouse model of Alzheimer’s disease, the authors show that Scara1 deficiency is associated with reduced clearance and increased deposition of aggregates in the brain, which results in early mortality.