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P1–345: Consequences of beta‐amyloid immunotherapy for Alzheimer's disease on neurons in the human cerebral cortex
Author(s) -
Boche Delphine,
Amin Jay,
MoutonLiger François,
Nasser Mariam,
Love Seth,
Gray Francoise,
Pickering Ruth,
Nicoll James,
Holmes Clive,
Hugon Jacques,
Paquet Claire
Publication year - 2013
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.2013.05.571
Subject(s) - neun , cortex (anatomy) , biology , pathology , entorhinal cortex , alzheimer's disease , senile plaques , neurofilament , neuropil , neuroscience , endocrinology , medicine , hippocampus , immunohistochemistry , central nervous system , disease
Background:Neuroinflammation, manifested by activation of microglia, is an important component of Alzheimer’s disease (AD) pathology with evidence to suggest that it is both a reaction to the disease process and a contributor to neuronal damage, promotingdisease progression. In this study, we have explored in detail the inflammatory processes in the human AD brain and compared the results with those obtained from patients following active Ab42 immunisation (Elan Pharmaceuticals, AN1792). Methods: We studied multiple brain regions in post-mortem tissue from 28 non-immunised AD patients and 11 AD patients immunised against Ab42 (up to 9 years prior to study). The antigen load was quantified in sections immunolabelled for microglial ionised calcium-binding adaptor molecule 1 (Iba-1), the lysosome marker CD68, macrophage scavenger receptor A (MSR-A), Fcg receptors I (CD64) and II (CD32), IgG, complement C1q and T lymphocytes, and compared to the amount of Ab and phospho-tau pathology. Results: The levels of CD68, MSR-A, CD64, CD32 loads and the number of MSR-A-positive plaque-related clusters were significantly lower in immunised AD than non-immunised cases, although there was no significant difference in Iba-1 load, number of Iba-1-positive cells, IgG load, C1q load or number of T cells. In non-immunized AD controls, Ab42 related inversely to CD32 and Iba-1, while phospho-tau was associated with all microglial markers, IgG, C1q and the total number of T cells. In immunised AD cases, Ab42 load related directly to MSR-A-positive clusters, and inversely to C1q.Conclusions:Our findings indicate that different microglial populations coexist in the AD brain and the local inflammatory response may provide an important link between Ab and tau pathology. After immunisation, the microglial functional state is altered in association with reduced Ab and tau pathology. The results suggest that, in the long term, Ab immunotherapy results in down-regulation of microglial activation and potentially reduces the inflammation-mediated component of neurodegeneration of AD.