References
Query Results -- Details
MGI Accession ID: MGI:3621689
J Number: J:107702
Other Accession IDs:
Title: ApoE and clusterin cooperatively suppress Abeta levels and deposition: evidence that ApoE regulates extracellular Abeta metabolism in vivo.
Authors: DeMattos RB; Cirrito JR; Parsadanian M; May PC; O'Dell MA; Taylor JW; Harmony JA; Aronow BJ; Bales KR; Paul SM; Holtzman DM
Journal: Neuron
Volume: 41
Issue: 2
Date: 2004 Jan 22
Year: 2004
Pages: 193-202
Review Status: Peer Reviewed
Abstract:
Apolipoprotein E (apoE) and clusterin can influence structure, toxicity, and accumulation of the amyloid-beta (Abeta) peptide in brain. Both molecules may also be involved in Abeta metabolism prior to its deposition. To assess this possibility, we compared PDAPP transgenic mice that develop age-dependent Abeta accumulation in the absence of apoE or clusterin as well as in the absence of both proteins. apoE(-/-) and clusterin(-/-) mice accumulated similar Abeta levels but much less fibrillar Abeta. In contrast, apoE(-/-)/clusterin(-/-) mice had both earlier onset and markedly increased Abeta and amyloid deposition. Both apoE(-/-) and apoE(-/-)/clusterin(-/-) mice had elevated CSF and brain interstitial fluid Abeta, as well as significant differences in the elimination half-life of interstitial fluid Abeta measured by in vivo microdialysis. These findings demonstrate additive effects of apoE and clusterin on influencing Abeta deposition and that apoE plays an important role in regulating extracellular CNS Abeta metabolism independent of Abeta synthesis.
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