Poster Presentations

Session Title: Inflammation
Presentation Date: Friday, March 14 – Saturday, March 15, 2009

ACTIVATION OF MICROGLIA IN ALZHEIMER'S DISEASE FOLLOWING Aβ42 IMMUNISATION: GOOD OR BAD?

D. Boche¹, E. Zotova¹, C. Holmes¹, J. Neal², D. Wilkinson³, J. Nicoll^1
1University of Southampton, Division of Clinical Neurosciences, Southampton, United Kingdom, ²University of Wales, Department of Pathology, Cardiff, United Kingdom, ³MARC Moorgreen Hospital, Southampton, United Kingdom

Background: Many studies have focused on microglial activation as a harmful feature of Alzheimer's disease (AD) with the implication that anti-inflammatory therapy may be beneficial. However, it has been shown that Aβ accumulation in the brain, a key feature of the disease, can be reversed by Aβ immunotherapy and that this effect is mediated, at least in part, by phagocytosis by microglia.
Material & methods: We have neuropathology on 9 AD patients who were actively immunised with Aβ42 peptide (iAD) in a clinical trial (Elan Pharmaceuticals). In these cases, we are exploring the expression of microglial proteins in relation to plaque removal and compared with unimmunised AD controls. Immunohistochemistry for HLA-DR and CD68 (a lysosomal protein, therefore demonstrating phagocytic activity) was performed in the frontal, temporal and parietal lobes (areas with AD pathology) and in the pons (an area without AD pathology).
Results: Quantification of HLA-DR load did not show a significant difference between the iAD cases vs AD controls. However, a significantly higher load of CD68 was observed after immunisation. In addition, CD68 load showed a significant correlation with Aβ42 load both in areas with and without AD pathology (i.e. cerebral cortex and pons).
Conclusions: Aβ42 immunisation alters the phenotype of microglia, increasing their capacity for phagocytosis. Interestingly, this change seems to take place not only in areas of the brain which contain Aβ plaques.