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Crehan H, Hardy J, Pocock J. Microglia, Alzheimer's disease, and complement. Int J Alzheimers Dis. 2012;2012:983640doi: 10.1155/2012/983640.
Crehan, H., Hardy, J., & Pocock, J. (2012). Microglia, Alzheimer's disease, and complement. International journal of Alzheimer's disease, 2012983640. https://doi.org/10.1155/2012/983640
Crehan, Helen, et al. "Microglia, Alzheimer's disease, and complement." International journal of Alzheimer's disease vol. 2012 (2012): 983640. doi: https://doi.org/10.1155/2012/983640
Crehan H, Hardy J, Pocock J. Microglia, Alzheimer's disease, and complement. Int J Alzheimers Dis. 2012;2012:983640. doi: 10.1155/2012/983640. Epub 2012 Aug 21. PMID: 22957298; PMCID: PMC3432348.
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Int J Alzheimers Dis. 2012;2012:983640. doi: 10.1155/2012/983640. Epub 2012 Aug 21.

Microglia, Alzheimer's disease, and complement.

International journal of Alzheimer's disease

Helen Crehan, John Hardy, Jennifer Pocock

Affiliations

  1. Department of Molecular Neurosciences, University College London Institute of Neurology, 1 Wakefield Street, London WC1N 1PJ, UK.

PMID: 22957298 PMCID: PMC3432348 DOI: 10.1155/2012/983640

Abstract

Microglia, the immune cell of the brain, are implicated in cascades leading to neuronal loss and cognitive decline in Alzheimer's disease (AD). Recent genome-wide association studies have indicated a number of risk factors for the development of late-onset AD. Two of these risk factors are an altered immune response and polymorphisms in complement receptor 1. In view of these findings, we discuss how complement signalling in the AD brain and microglial responses in AD intersect. Dysregulation of the complement cascade, either by changes in receptor expression, enhanced activation of different complement pathways or imbalances between complement factor production and complement cascade inhibitors may all contribute to the involvement of complement in AD. Altered complement signalling may reduce the ability of microglia to phagocytose apoptotic cells and clear amyloid beta peptides, modulate the expression by microglia of complement components and receptors, promote complement factor production by plaque-associated cytokines derived from activated microglia and astrocytes, and disrupt complement inhibitor production. The evidence presented here indicates that microglia in AD are influenced by complement factors to adopt protective or harmful phenotypes and the challenge ahead lies in understanding how this can be manipulated to therapeutic advantage to treat late onset AD.

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