title: Adult mouse astrocytes degrade amyloid-beta in vitro and in situ.
abstract: Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by excessive deposition of amyloid-beta (Abeta) peptides in the brain. One of the earliest neuropathological changes in AD is the accumulation of astrocytes at sites of Abeta deposition, 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 lesions, and cease migration upon interaction with immobilized Abeta(1-42). We also show that astrocytes bind and degrade Abeta(1-42). Astrocytes plated on Abeta-laden brain sections from a mouse model of AD associate with the Abeta deposits and reduce overall Abeta levels in these sections. Our results suggest a novel mechanism for the accumulation of astrocytes around Abeta deposits, indicate a direct role for astrocytes in degradation of Abeta and implicate deficits in astroglial clearance of Abeta in the pathogenesis of AD. Treatments that increase removal of Abeta by astrocytes may therefore be a critical mechanism to reduce the neurodegeneration associated with AD.
authors.affiliation: Geriatric Research, Education and Clinical Center, VA Palo Alto Health Care System, Palo Alto, California, USA.
authors.forename: Tony
authors.initials: T
authors.lastname: Wyss-Coray
authors.forename: John D
authors.initials: JD
authors.lastname: Loike
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Brionne
authors.forename: Emily
authors.initials: E
authors.lastname: Lu
authors.forename: Roman
authors.initials: R
authors.lastname: Anankov
authors.forename: Fengrong
authors.initials: F
authors.lastname: Yan
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Silverstein
authors.forename: Jens
authors.initials: J
authors.lastname: Husemann
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism*; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000494:pharmacology; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D018932:Chemokine CCL2; D010446:Peptide Fragments; C092862:amyloid beta-protein (10-43)