Adult mouse astrocytes degrade amyloid-β in vitro and in situ

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Abstract
Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by excessive deposition of amyloid-β (Aβ) peptides in the brain. One of the earliest neuropathological changes in AD is the accumulation of astrocytes at sites of Aβ 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 Aβ1–42. We also show that astrocytes bind and degrade Aβ1–42. Astrocytes plated on Aβ-laden brain sections from a mouse model of AD associate with the Aβ deposits and reduce overall Aβ levels in these sections. Our results suggest a novel mechanism for the accumulation of astrocytes around Aβ deposits, indicate a direct role for astrocytes in degradation of Aβ and implicate deficits in astroglial clearance of Aβ in the pathogenesis of AD. Treatments that increase removal of Aβ by astrocytes may therefore be a critical mechanism to reduce the neurodegeneration associated with AD.