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

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Description/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 β-peptide (Aβ) has been proposed as a novel treatment for AD. Experimental models have shown that Aβ 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 Aβ immunotherapy runs by Elan Pharmaceuticals which started in 2000. Immunohistochemical study of the immunized AD cases examined to date (n=8) shows that the Aβ plaque removal varies from patchy to almost complete clearance. Doublelabel confocal microscopy was performed with antibody to Aβ 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 Aβ within the lysosomes of activated microglia, indicating that the Aβ has been phagocytosed. In cases of unimmunized AD there was microglial activation, but very little evidence of Aβ 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

Item Type: Conference or Workshop Item (Paper)
Additional Information: Paper PP23-05
ISSNs: 0165-5728 (print)
Keywords: immunotherapy, alzheimer's disease, disease
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
R Medicine > RM Therapeutics. Pharmacology
Divisions: University Structure - Pre August 2011 > School of Biological Sciences
University Structure - Pre August 2011 > School of Medicine
ePrint ID: 62326
Date Deposited: 12 Sep 2008
Last Modified: 27 Mar 2014 18:44
URI: http://eprints.soton.ac.uk/id/eprint/62326

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