The University of Southampton
University of Southampton Institutional Repository

Neuroinflammation and Alzheimer's disease: implications of Abeta immunotherapy

Neuroinflammation and Alzheimer's disease: implications of Abeta immunotherapy
Neuroinflammation and Alzheimer's disease: implications of Abeta immunotherapy
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
immunotherapy, alzheimer's disease, disease
267-268
Boche, D.
bdcca10e-6302-4dd0-919f-67218f7e0d61
Holmes, C.
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Perry, VH.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Vlachouli, C.
2ea2d3df-7579-4262-a8e8-0b58e0b5064d
Thompson, P.
0a0015a4-61ee-473c-9e4b-8afca6adff45
Nicoll, J.A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Boche, D.
bdcca10e-6302-4dd0-919f-67218f7e0d61
Holmes, C.
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Perry, VH.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Vlachouli, C.
2ea2d3df-7579-4262-a8e8-0b58e0b5064d
Thompson, P.
0a0015a4-61ee-473c-9e4b-8afca6adff45
Nicoll, J.A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed

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).

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

This record has no associated files available for download.

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 C. Holmes: ORCID iD orcid.org/0000-0003-1999-6912
ORCID for J.A.R. Nicoll: ORCID iD orcid.org/0000-0002-9444-7246

Catalogue record

Date deposited: 12 Sep 2008
Last modified: 16 Mar 2024 03:26

Export record

Altmetrics

Contributors

Author: D. Boche ORCID iD
Author: C. Holmes ORCID iD
Author: VH. Perry
Author: C. Vlachouli
Author: P. Thompson
Author: J.A.R. Nicoll ORCID iD

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×