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Complement activation fragment C5a receptors, CD88 and C5L2, are associated with neurofibrillary pathology

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Title: Complement activation fragment C5a receptors, CD88 and C5L2, are associated with neurofibrillary pathology
Author(s): Fonseca, Maria I.; McGuire, Susan O.; Counts, Scott E.; Tenner, Andrea J.
Subject(s): C5a receptors CD88 C5L2
Abstract: Background: Alzheimer's disease (AD) is a neurodegenerative dementia characterized by the decline of cognition and the presence of neuropathological changes including neuronal loss, neurofibrillary pathology and extracellular senile plaques. A neuroinflammatory process is also triggered and complement activation has been hypothesized to have a relevant role in this local inflammatory response. C5a, a proinflammatory anaphylatoxin generated after complement activation, exerts its chemotactic and inflammatory functions through the CD88 receptor while the more recently discovered C5L2 receptor has been postulated to have an anti-inflammatory role. Previously, we reported that a CD88 specific antagonist (PMX205) decreased the pathology and improved cognition in transgenic models of AD suggesting that C5a/C5aR interaction has an important role in the progression of the disease. Methods: The present study characterizes the expression of the two receptors for C5a in human brain with confirmed post mortem diagnosis of vascular dementia (VD) or AD as well as age matched controls by immunohistochemistry and Western blot analysis using several antibodies against different epitopes of the human receptors. Results: The CD88 and C5L2 antibodies revealed increased expression of both receptors in AD samples as compared to age-matched controls or VD brain tissue by Western blot and immunohistochemistry, using multiple antibodies and distinct cohorts of brain tissue. Immunostaining showed that both the C5L2 and CD88 antibodies similarly labeled abundant neurofibrillary tangles, neuropil threads and dystrophic neurites associated with plaques in the hippocampus and frontal cortex of AD cases. In contrast, little or no neuronal staining, tangles or dystrophic neurites associated with plaques were observed in control or VD brains. CD88 and C5L2 receptors are associated with both early (AT8) and mature (PHF1) neurofibrillary tangles and can be found either independently or colocalized with each other. Conclusions: The observed association of CD88 and C5L2 with neurofibrillary pathology suggests a common altered pathway of degradation.
Issue Date: 2013-02
Publisher: BioMed Central
Citation Info: Fonseca, M. I., McGuire, S. O., Counts, S. E. and Tenner, A. J. Complement activation fragment C5a receptors, CD88 and C5L2, are associated with neurofibrillary pathology. Journal of Neuroinflammation. 2013. 10. DOI: 10.1186/1742-2094-10-25
Type: Article
Description: © 2013 Fonseca et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 by BioMed Central, Journal of Neuroinflammation
URI: http://hdl.handle.net/10027/11043
ISSN: 1742-2094
Sponsor: This work was supported by NIH grants NS35144 and AG 00538 to AT and a grant from the Alzheimer’s Association, IIRG-08-91605, to SM.
Date Available in INDIGO: 2014-01-09
 

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