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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 At 8th International Conference of Neuroimmunology (ISNI 2006). , pp. 267-268. (doi:10.1016/j.jneuroim.2006.07.002).

Record type: Conference or Workshop Item (Paper)

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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More information

Published date: September 2006
Additional Information: Paper PP23-05
Venue - Dates: 8th International Conference of Neuroimmunology (ISNI 2006), 2006-09-01
Keywords: immunotherapy, alzheimer's disease, disease
Organisations: Biological Sciences, Medicine

Identifiers

Local EPrints ID: 62326
URI: http://eprints.soton.ac.uk/id/eprint/62326
PURE UUID: ad4a7344-9c48-4ef5-94b7-8289bdd8c472
ORCID for D. Boche: ORCID iD orcid.org/0000-0002-5884-130X
ORCID for J.A.R. Nicoll: ORCID iD orcid.org/0000-0002-9444-7246

Catalogue record

Date deposited: 12 Sep 2008
Last modified: 17 Jul 2017 14:20

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