Die Rolle des Immunsystems bei der Alzheimer-Demenz

J. Alferink

doi:10.1055/s-0038-1626938

Nervenheilkunde, Inhaltsverzeichnis

Nervenheilkunde 2007; 26(10): 867-875
DOI: 10.1055/s-0038-1626938

Arbeiten zum Schwerpunkt - Theme Articles

Schattauer GmbH

Die Rolle des Immunsystems bei der Alzheimer-Demenz

The immune response in Alzheimer’s Disease

J. Alferink

¹Klinik und Poliklinik für Psychiatrie und Psychotherapie des Universitätsklinikums Bonn (Direktor: Prof. Dr. med. W. Maier), Institut für molekulare Psychiatrie, Life and Brain, Bonn (Direktor: Prof. Dr. rer. nat. A. Zimmer)

› Institutsangaben

Abstract

Zusammenfassung

Die Alzheimer-Demenz (AD) ist eine primär neurodegenerative Erkrankung, die zu einem fortschreitenden Verlust kognitiv-mnestischer Funktionen führt. Im Alzheimergehirn zeigen sich neben einem progredienten Neuronenuntergang neuropathologisch charakteristische Proteinablagerungen in Form sogenannter Alzheimerplaques und intrazellulärer Fibrillenbündel. Bei diesen Prozessen scheint das Immunsystem eine zentrale Rolle zu spielen. In post mortem Alzheimerhirngeweben und im Gehirn von Alzheimermausmodellen tritt eine durch Mikrogliazellen vermittelte Entzündungsreaktion auf. Es gibt Hinweise, dass diese aktivierten “Gehirn-Makrophagen” durch die Sekretion proinflammatorischer Zytokine und zytotoxischer Faktoren den neurodegenerativen Prozess verstärken. Andererseits können Mikrogliazellen durch die Produktion von Wachstumsfaktoren und neuroprotektiven Zytokinen Neurone vor dem Zelluntergang schützen. Insbesondere Mikrogliazellen, die aus dem peripheren Blut in das Gehirn einwandern, scheinen die Aβ-Akkumulation in einem AD-Mausmodell unter- drücken zu können. Die aktuellen Befunde über eine pathologisch relevante Implikation dieser Mikrogliazellen lassen auf die Aufklärung therapierelevanter, auf den Menschen übertragbarer Immunmechanismen hoffen.

Summary

Alzheimer’s disease is a primary neurodegenerative disease, leading to the chronic progredient loss of cognitivemnestic functions. Neuropathological hallmarks of the Alzheimer-brain are a progressive neuronal cell death and the deposition of abnormal proteins in so-called Alzheimerplaques and neurofibrillary tangles. The immune system seems to play a crucial role in these processes. In postmortem Alzheimer brain-tissue and in the brains of Alzheimer mouse models a microglia-mediated inflammatory immune reaction can be observed. There is evidence that activation of these “brain-macrophages” aggravates the neurodegenerative process through their secretion of proinflammatory cytokines and cytotoxic factors. On the other hand microglia can protect neurons from cell death by the production of growth factors and neuroprotective cytokines. In particular, microglia immigrating from the peripheral blood into the brain seem to be capable of suppressing Aβ-accumulation in an AD mouse model. The elucidation of these newly discovered immunomechanisms are of great importance due to their straight conferability to human AD and promising therapeutic implications.

Schlüsselwörter

Alzheimer-Erkrankung - Immunantwort - Mikrogliazellen - antigenpräsentierende Zellen - T-Zellen

Keywords

Alzheimer’s disease - adaptive immune response - microglia - antigen-presenting cells - T-cells

Volltext

Referenzen

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