Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by excessive deposition of amyloid- (A) peptides in the brain. One of the earliest neuropathological changes in AD is the accumulation of astrocytes at sites of A deposition1, but the cause or significance of this cellular response is unclear. Here we show that cultured adult mouse astrocytes migrate in response to monocyte chemoattractant protein-1 (MCP-1), a chemokine present in AD lesions1, and cease migration upon interaction with immobilized A1−42. We also show that astrocytes bind and degrade A1−42. Astrocytes plated on A-laden brain sections from a mouse model of AD associate with the A deposits and reduce overall A levels in these sections. Our results suggest a novel mechanism for the accumulation of astrocytes around A deposits, indicate a direct role for astrocytes in degradation of A and implicate deficits in astroglial clearance of A in the pathogenesis of AD. Treatments that increase removal of A by astrocytes may therefore be a critical mechanism to reduce the neurodegeneration associated with AD.
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
in vitro and in situ
(A
1 promotes microglial amyloid-
