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Autoantibodies against beta-amyloid are common in Alzheimer's disease and help control plaque burden


Kellner, A; Matschke, J; Bernreuther, C; Moch, H; Ferrer, I; Glatzel, M (2009). Autoantibodies against beta-amyloid are common in Alzheimer's disease and help control plaque burden. Annals of Neurology, 65(1):24-31.

Abstract

OBJECTIVE: Active or passive immunization of Alzheimer's disease (AD) patients leads to targeting of beta-amyloid plaques by immunoglobulins (IgG) and their subsequent removal by microglia. Here, we investigate whether naturally occurring autoantibodies to beta-amyloid contribute to beta-amyloid plaque removal in nonimmunized AD patients. METHODS: We generated an AD tissue microarray with 2,325 tissue specimens from 3 defined central nervous system regions of 48 AD patients and 48 age-matched control patients. Absolute quantification of beta-amyloid, beta-amyloid plaque-bound IgG, and phagocytic, resting, and activated microglia and microhemorrhages was done using a standardized, highly reproducible scoring system. RESULTS: The majority of neuritic plaques are decorated by IgG. AD patients with prominently IgG-labeled neuritic plaques have a significantly reduced plaque burden and an increase in phagocytic microglia, yet no increase in microhemorrhages. INTERPRETATION: Autoantibodies directed against beta-amyloid are common in AD patients and may contribute in controlling plaque burden.

Abstract

OBJECTIVE: Active or passive immunization of Alzheimer's disease (AD) patients leads to targeting of beta-amyloid plaques by immunoglobulins (IgG) and their subsequent removal by microglia. Here, we investigate whether naturally occurring autoantibodies to beta-amyloid contribute to beta-amyloid plaque removal in nonimmunized AD patients. METHODS: We generated an AD tissue microarray with 2,325 tissue specimens from 3 defined central nervous system regions of 48 AD patients and 48 age-matched control patients. Absolute quantification of beta-amyloid, beta-amyloid plaque-bound IgG, and phagocytic, resting, and activated microglia and microhemorrhages was done using a standardized, highly reproducible scoring system. RESULTS: The majority of neuritic plaques are decorated by IgG. AD patients with prominently IgG-labeled neuritic plaques have a significantly reduced plaque burden and an increase in phagocytic microglia, yet no increase in microhemorrhages. INTERPRETATION: Autoantibodies directed against beta-amyloid are common in AD patients and may contribute in controlling plaque burden.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2009
Deposited On:16 Dec 2009 08:45
Last Modified:21 Nov 2017 14:32
Publisher:Wiley-Blackwell
ISSN:0364-5134
Additional Information:The definitive version is available at www.blackwell-synergy.com
Publisher DOI:https://doi.org/10.1002/ana.21475
PubMed ID:19194878

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