Microglial C5aR (CD88) expression correlates with amyloid-β deposition in murine models of Alzheimer's disease

Ager, Rahasson R., Fonseca, Maira I., Chu, Shu-Hui, Sanderson, Sam D., Taylor, Stephen M., Woodruff, Trent M. and Tenner, Andrea J. (2010) Microglial C5aR (CD88) expression correlates with amyloid-β deposition in murine models of Alzheimer's disease. Journal of Neurochemistry, 113 2: 389-401. doi:10.1111/j.1471-4159.2010.06595.x


Author Ager, Rahasson R.
Fonseca, Maira I.
Chu, Shu-Hui
Sanderson, Sam D.
Taylor, Stephen M.
Woodruff, Trent M.
Tenner, Andrea J.
Title Microglial C5aR (CD88) expression correlates with amyloid-β deposition in murine models of Alzheimer's disease
Journal name Journal of Neurochemistry   Check publisher's open access policy
ISSN 0022-3042
Publication date 2010-04
Sub-type Article (original research)
DOI 10.1111/j.1471-4159.2010.06595.x
Volume 113
Issue 2
Start page 389
End page 401
Total pages 13
Place of publication Oxford, United Kingdom
Publisher Wiley-Blackwell Publishing
Collection year 2011
Language eng
Subject C1
920112 Neurodegenerative Disorders Related to Ageing
060110 Receptors and Membrane Biology
Abstract Alzheimer’s disease (AD), a progressive neurodegenerative disease characterized by the accumulation of amyloid-β protein and neuronal loss, is the leading cause of age-related dementia in the world today. The disease is also associated with neuroinflammation, robust activation of astrocytes and microglia, and evidence of activation of the complement system, localized with both fibrillar amyloid-β (fAβ) plaques and tangles. The observations are consistent with a complement-dependent component of AD progression. We have previously shown that inhibition of the major complement receptor for C5a (CD88) with the antagonist PMX205 results in a significant reduction in pathology in two mouse models of AD. To further characterize the role of complement in AD-related neuroinflammation, we examined the age- and disease-associated expression of CD88 in brain of transgenic mouse models of AD and the influence of PMX205 on the presence of various complement activation products using flow cytometry, western blot, and immunohistochemistry. CD88 was found to be up-regulated in microglia, in the immediate vicinity of amyloid plaques. While thioflavine plaque load and glial recruitment is significantly reduced after treatment with PMX205, C1q remains co-localized with fAβ plaques and C3 is still expressed by the recruited astrocytes. Thus, with PMX205, potentially beneficial activities of these early complement components may remain intact, while detrimental activities resulting from C5a–CD88 interaction are inhibited. This further supports the targeted inhibition of specific complement mediated activities as an approach for AD therapy. Copyright © 1999–2011 John Wiley & Sons, Inc. All Rights Reserved.
Keyword Alzheimer's Disease
C5a receptor
Complement
Microglia
Murine models
Neuroinflammation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Biomedical Sciences Publications
 
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Created: Sun, 04 Apr 2010, 00:03:19 EST