Possible role of scavenger receptor SRCL in the clearance of amyloid‐βin Alzheimer's disease

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Abstract
Accumulation of β‐amyloid protein (Aβ) in the brain is a hallmark of Alzheimer's disease (AD), and Aβ‐mediated pathogenesis could result from increased production of Aβ or insufficient Aβ clearance by microglia, astrocytes, or the vascular system. Cell‐surface receptors, such as scavenger receptors, might play a critical role in the binding and clearing of Aβ; however, the responsible receptors have yet to be identified. We show that scavenger receptor with C‐type lectin (SRCL), a member of the scavenger receptor family containing coiled‐coil, collagen‐like, and C‐type lectin/carbohydrate recognition domains, is expressed in cultured astrocytes and microglia. In contrast to the low expression of SRCL in the wild‐type mouse brain, in a double transgenic mouse model of AD (Tg‐APP/PS1), immunohistochemistry showed that SRCL was markedly induced in Aβ‐positive astrocytes and Aβ‐positive vascular/perivascular cells, which are associated closely with cerebral amyloid angiopathy. In patients with AD, the distribution of SRCL was similar to that seen in the Tg‐APP/PS1 temporal cortex. The presence of a large number of SRCL/Aβ double‐positive particles in the intracellular compartments of reactive astrocytes and vascular/perivascular cells in Tg‐APP/PS1 mice and AD patients suggests a role for SRCL in Aβ clearance. Moreover, CHO‐K1 cells transfected with SRCL isoforms were found to bind fibrillar Aβ1–42. These findings suggest that SRCL could be the receptor involved in the binding or clearing of Aβ by glial and vascular/perivascular cells in AD.