Reduced β-amyloid pathology in an APP transgenic mouse model of Alzheimer’s disease lacking functional B and T cellsReport as inadecuate




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Acta Neuropathologica Communications

, 3:71

First Online: 11 November 2015Received: 02 November 2015Accepted: 02 November 2015

Abstract

IntroductionIn Alzheimer’s disease, accumulation and pathological aggregation of amyloid β-peptide is accompanied by the induction of complex immune responses, which have been attributed both beneficial and detrimental properties. Such responses implicate various cell types of the innate and adaptive arm of the immunesystem, both inside the central nervous system, and in the periphery. To investigate the role of the adaptive immune system in brain β-amyloidosis, PSAPP transgenic mice, an established mouse model of Alzheimer’s disease, were crossbred with the recombination activating gene-2 knockout Rag2 ko mice lacking functional B and T cells. In a second experimental paradigm, aged PSAPP mice were reconstituted with bone marrow cells from either Rag2 ko or wildtype control mice.

ResultsAnalyses from both experimental approaches revealed reduced β-amyloid pathology and decreased brain amyloid β-peptide levels in PSAPP mice lacking functional adaptive immune cells. The decrease in brain β-amyloid pathology was associated with enhanced microgliosis and increased phagocytosis of amyloid β-peptide aggregates.

ConclusionThe results of this study demonstrate an impact of the adaptive immunity on cerebral β-amyloid pathology in vivo and suggest an influence on microglia-mediated amyloid β-peptide clearance as a possible underlying mechanism.

KeywordsAlzheimer’s disease Adaptive immunity Amyloid β-peptide Rag2 knockout mice Microglia Electronic supplementary materialThe online version of this article doi:10.1186-s40478-015-0251-x contains supplementary material, which is available to authorized users.

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Author: Claudia Späni - Tobias Suter - Rebecca Derungs - Maria Teresa Ferretti - Tobias Welt - Fabian Wirth - Christoph Gericke -

Source: https://link.springer.com/







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