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Fortschr Neurol Psychiatr 2003; 71: 16-26
DOI: 10.1055/s-2003-40501
Originalarbeit
© Georg Thieme Verlag Stuttgart · New York

Pathomechanismen und hypothesengeleitete Therapieoptionen bei der Spätform der Alzheimer-Krankheit

Pathomechanisms and Hypothesis-Guided Therapeutic Strategies for Late-Onset Alzheimer's DiseaseS.  Hoyer1 , P.  Riederer2
  • 1Abteilung für Pathochemie und Allgemeine Neurochemie, Universität Heidelberg
  • 2Klinische Neurochemie, Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universität Würzburg und NPF Center of Excellence Research Laboratories
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Publication History

Publication Date:
08 July 2003 (online)

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Zusammenfassung

Obwohl die klinische Wirksamkeit der in der gegenwärtigen Therapie der sporadischen AK eingesetzten Pharmaka ausreichend belegt erscheint, sind ihre Wirkungsmechanismen weit weniger gut bekannt oder werden bei der Beurteilung der klinischen Effekte außer Acht gelassen. Es erscheint jedoch unumgänglich, klinische Wirkung und Wirkungsmechanismen von Pharmaka zu kennen, um ihren Schaden und Nutzen zu beurteilen. Hinsichtlich der bei der sporadischen AK in der Bundesrepublik Deutschland zur Anwendung kommenden Pharmaka zeigen sich völlig unterschiedliche Wirkungsmechanismen. Unter Berücksichtigung der dargestellten Pathomechanismen, die bei sporadischer AK in unterschiedlicher Weise bekannt geworden sind, ergibt sich eine therapeutische Rationale für einen Einsatz von Ginkgo-biloba-Extrakt (EGb 761) und Memantin. Die Anwendung von Azetylcholinesterasehemmern, die vielfach als Mittel der Wahl angesehen werden, ist wegen der Gefahr des Auftretens myopathischer Störungen bzw. des Gulf-War-Syndroms als kritisch zu betrachten. Als viel versprechend apostrophierte und vorschnell propagierte Therapiestrategien mit Statinen oder Vaccination gegen βA4 sollten wegen fehlender Angriffspunkte im bekannten pathophysiologischen Schädigungsmuster der sporadischen AK nicht angewendet werden. Zukünftige Entwicklungen müssten berücksichtigen, dass bei der sporadischen AK nicht oder nur schwer zu therapierende Alterseinflüsse vorliegen. Therapieziele sollten in der Verbesserung des zellulären Energiestatus und der Membranfunktion bestehen.

Abstract

Even though the clinical effectiveness of the presently used pharmaceutical therapy of sporadic Alzheimer Disease seems to be proven sufficient, their effective mechanisms are much less known or are disregarded in the evaluation of the clinical effects. However, it seems to be inevitable to know both clinical effect and effective mechanisms of pharmaceutics in order to be able to judge their adversity and benefit. In reference to the pharmaceutics implemented on sporadic AD in Germany, total different effective mechanisms are shown. In consideration of the shown pathomechanisms which have been recognized for sporadic AD, therapeutic rationales on application of Ginkgo biloba extract (EGb 761) and Memantine are evident. The application of acetylcholinesterase inhibitors, often looked on as agent of choice, is to be considered critically because of the danger of the occurrence of myopathical dysfunction, resp. the Gulf War Syndrome. Sophisticated and hastily advertised therapy strategies with statines or vaccination against βA4 should not be used because of a lack of sufficient evidence based on the pathophysiological pattern of damage as known in sporadic AD. Future development must take in account that with sporadic AD aging influences cannot or can hardly be influenced. Therapeutic goals should consist to improve the cellular energy status and the membrane functioning.

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Prof. Dr. Peter Riederer

Klinik und Poliklinik für Psychiatrie und Psychotherapie · Klinische Neurochemie

Füchsleinstr. 15

97080 Würzburg

Email: peter.riederer@mail.uni-wuerzburg.de

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