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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

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

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

Nature communications 20130101

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 ...[more]

PMID: 23799536

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