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O2‐03–07: Inhibition of microglia activation prevents fibrillar amyloid‐beta toxicity in the aged rhesus cortex
Author(s) -
Guo Ling,
Leung Elaine,
Bu Jing,
El-Khoury Joseph,
Geula Changiz
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.328
Subject(s) - microglia , senile plaques , cortex (anatomy) , neurotoxicity , biology , pathology , immunology , toxicity , chemistry , alzheimer's disease , medicine , neuroscience , inflammation , disease
with amyloid -peptide (A ) has been proposed as a 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 (cells of the monocyte/macrophage lineage). Methods: We are co-ordinating a collaborative clinical and neuropathological follow-up of the patients who where in the first trial of active A immunization (Elan Pharmaceuticals). To date we have neuropathology on 9 immunized AD patients (iAD) who died between 4 and 64 months after first immunization dose. In these cases we have quantified the expression of microglial proteins, compared with unimmunized AD controls. Results: CD68 is a component of the wall of lysosomes and its presence is therefore an indication of phagocytic activity. A similar amount of CD68 immunostaining was observed in cerebral cortex of both the iAD cases and AD controls indicating phagocytic activity in both groups. The iAD cases showed variable degrees of plaque clearance associated with A within the lysosomes of activated microglia, indicating that A had been phagocytosed. However, the phagocytic activity in the AD controls was not associated with A within microglia, suggesting that microglia are qualitatively different after immunization. Conclusions: These observations highlight the point that, rather than simply demonstrating that microglia have been activated, it is the specific way in which microglia are activated that is important in determining their role in AD pathology. To what extent the changes in the activation of microglia are reflected in changes in cognitive function, remains to be determined. Indeed despite evidence of plaque removal, mediated at least in part by microglia, all except one of the iAD patients studied at post mortem had severe end stage dementia prior to death.