Journal Article

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

Kingery, Nathan D, Means, Terry K, Frenkel, Dan, Wilkinson, Kim, El Khoury, Joseph, Farfara, Dorit, Weiner, Howard L, Zhao, Lingzhi, Puckett, Lindsay, Hickman, Suzanne E

2013

نظرة عامة

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.

• الناشر: Nature Publishing Group
• موضوع: Alzheimer's disease