Neuroinflammation and Alzheimer's disease: implications of Abeta immunotherapy

Boche, D., Holmes, C., Perry, VH., Vlachouli, C., Thompson, P. and Nicoll, J.A.R. (2006) Neuroinflammation and Alzheimer's disease: implications of Abeta immunotherapy. 8th International Conference of Neuroimmunology (ISNI 2006). pp. 267-268 . (doi:10.1016/j.jneuroim.2006.07.002).

Abstract

Alzheimer's disease (AD) is the commonest cause of dementia in ageing. Over the past decade many studies have focused on neuroinflammation as a harmful feature of AD, with the implication that antiinflammatory therapy may be beneficial. More recently, immunization with amyloid ?-peptide (A?) has been proposed as a novel treatment for AD. Experimental models have shown that A? accumulation in the brain, a key feature of the disease, can be reversed by immunotherapy mediated, at least in part, by phagocytosis by microglia, the cerebral macrophage. We are co-ordinating collaborative clinical and neuropathological follow-up of the patients who where in the original trial of A? immunotherapy runs by Elan Pharmaceuticals which started in 2000. Immunohistochemical study of the immunized AD cases examined to date (n=8) shows that the A? plaque removal varies from patchy to almost complete clearance. Doublelabel confocal microscopy was performed with antibody to A? and either CD68 (PG-M1; a protein located on microglial lysosomes which therefore reflects phagocytic activity) or HLA-DR (CR3/43; MHC class II). This showed that plaque removal is associated with the presence of A? within the lysosomes of activated microglia, indicating that the A? has been phagocytosed. In cases of unimmunized AD there was microglial activation, but very little evidence of A? phagocytosis. These observations are in contrast to previous evidence that microglial activation in neurodegenerative disorders is only harmful, and suggest that microglial activation represents a two-edged sword with both harmful and potentially beneficial effects

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Contributors

Author: D. Boche

Author: C. Holmes

Author: J.A.R. Nicoll

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