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Der Nervenarzt

, Volume 79, Supplement 3, pp 117–128 | Cite as

Alzheimer-Demenz

Molekulare Pathologie, Tiermodelle und Therapiestrategien
  • T. A. Bayer
  • O. Wirths
CME Weiterbildung - Zertifizierte Fortbildung
  • 585 Downloads

Zusammenfassung

Die bisher gegen Alzheimer-Demenz (AD) zugelassenen und wenig wirksamen Medikamente behandeln nur Symptome. Genetische, neuropathologische und biochemische Daten unterstreichen die Bedeutung der Amyloidhypothese der AD, aus der neue Forschungsansätze mit krankheitsmodifizierendem Potenzial resultieren. Viele Behandlungsstrategien sind auf dieser Grundlage in präklinischen Tiermodellen erfolgreich durchgeführt worden. Allerdings steht ein Behandlungserfolg bei AD-Patienten leider noch aus. Ursächlich hierfür ist wahrscheinlich, dass die bisher genutzten Tiermodelle nur geringe Verhaltensdefizite und keinen Alzheimer-ähnlichen Nervenzellverlust zeigen, obwohl sie alle mehr oder weniger viele Plaques ausbilden. Wir wissen heute, dass die Alzheimer-Plaques nicht hauptsächlich für den Zelltod verantwortlich sind. Neu entwickelte Tiermodelle zeigen eine altersabhängige axonale Degeneration, massiven Nervenzellverlust und robuste Verhaltensdefizite. Behandlungen, die bei diesen Tiermodellen mit solch robusten Defiziten erfolgreich wären, ließen sich besser in die Klinik übertragen. Die abschließende Validierung oder Falsifizierung bestimmter Alzheimer-Hypothesen und darauf beruhende Behandlungsstrategien können jedoch nur durch eine klinische Prüfung erfolgen.

Schlüsselbegriffe

Intraneuronales Aβ42 Amyloid Transgene Mäuse Neurodegeneration Behandlung 

Alzheimer’s disease

Molecular pathology, animal models, and current treatment

Summary

The currently approved but only mildly efficient drugs against Alzheimer’s disease treat merely the symptoms. Genetic, neuropathological, and biochemical data support the importance of the amyloid hypothesis of Alzheimer’s disease, at the moment the most influential hypothesis. Many treatment strategies have been performed based on this hypothesis and were markedly successful in preclinical animal models. Unfortunately the treatment is still unsuccessful in humans. This could be due to the animal models showing marginal behavioural deficits but no Alzheimer-like nerve cell loss, although they all developed a more or less pronounced plaque load. Today we know however that Alzheimer plaques are not mainly responsible for the cell loss. Therefore novel animal models have been developed that show age-dependent axonal degeneration, massive neuronal loss, and robust behavioural deficits. Successful treatment of an animal model with such robust deficits would be very likely better suited to transferral into the clinic. The final validation or disproof of individual Alzheimer hypotheses and their resulting treatment strategies can however be obtained only after clinical proof.

Keywords

Intraneuronal Aβ42 Amyloid Transgenic mice Neurodegeneration Treatment 

Notes

Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehung hin: Der korrespondierende Autor ist Mitglied im wissenschaftlichen Beirat der Probiodrug AG, Halle/Saale.

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Copyright information

© Springer Medizin Verlag 2008

Authors and Affiliations

  1. 1.Klinik für PsychiatrieUniversitätsmedizin GöttingenGöttingenDeutschland

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