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Der Nervenarzt

, Volume 87, Issue 11, pp 1163–1174 | Cite as

Mechanismen der Alzheimer-Krankheit

Neuronale Hyper- und Hypoaktivität als neue Therapieziele
  • M. A. BuscheEmail author
  • M. Staufenbiel
  • M. Willem
  • C. Haass
  • H. Förstl
Übersichten

Zusammenfassung

Die Alzheimer-Krankheit ist gekennzeichnet durch die pathologische Ablagerung von Amyloid-β (Aβ) und Tau im Gehirn. Zusätzlich könnte das neu entdeckte Aeta (Aη) eine wichtige Rolle in der Pathogenese spielen. Die Aufklärung der neurophysiologischen Mechanismen der Alzheimer-Krankheit hat einige überraschende Erkenntnisse erbracht, die für die Frühestidentifikation von Personen mit Alzheimer-Krankheit und die Entwicklung neuer Therapien von großer Bedeutung sein können. Funktionsanalysen auf verschiedenen Ebenen, von einzelnen Neuronen bis hin zu großen Netzwerken im intakten Gehirn in vivo zeigen nämlich, dass Aβ, Tau und Aη Gehirnaktivität abnorm modulieren und dabei offensichtlich gegensätzliche Wirkungen entfalten: Während Aβ Hyperaktivität und sogar zerebrale Anfälle verursacht, führen Tau und Aη zu einer neuronalen Hypoaktivität. Erste klinische Untersuchungen deuten darauf hin, dass die Therapie von Hyperaktivität kognitive Funktionen verbessern und den Verlauf der Alzheimer-Krankheit günstig beeinflussen könnte.

Schlüsselwörter

Morbus Alzheimer Amyloid-β Tau-Peptid Neuronen Kognitive Funktion 

Mechanisms of Alzheimer’s disease

Neuronal hyperactivity and hypoactivity as new therapeutic targets

Abstract

Alzheimer’s disease (AD) is characterized by the pathological accumulation of amyloid-beta (Abeta) and tau peptides in the brain. Recent evidence suggests that the soluble peptide amyloid-eta (Aeta) may have an additional role in the pathogenesis of AD. The detailed investigation of the cellular and neurophysiological mechanisms underlying AD has revealed surprising results that may become highly relevant for the early diagnosis and treatment of the disease. By analyzing the function of single neurons and large-scale networks in intact brains in vivo it has been shown that A-beta, tau and A-eta abnormally modulate brain activity and obviously unfold contrasting effects: while A-beta promotes neuronal hyperactivity as well as epileptiform activity, tau and A-eta reduce the activity of neurons. Promising new evidence from animal studies and humans with AD indicates that the treatment of hyperactivity may improve cognitive dysfunctions and even slow the underlying disease process.

Keywords

Alzheimer’s disease Amyloid-beta Tau peptides Neurons Cognitive function 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

M.A. Busche, M. Staufenbiel, M. Willem, C. Haass und H. Förstl geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • M. A. Busche
    • 1
    • 2
    • 3
    Email author
  • M. Staufenbiel
    • 4
  • M. Willem
    • 5
    • 6
  • C. Haass
    • 3
    • 5
    • 6
  • H. Förstl
    • 1
  1. 1.Klinik und Poliklinik für Psychiatrie und PsychotherapieTechnische Universität MünchenMünchenDeutschland
  2. 2.Institut für NeurowissenschaftenTechnische Universität MünchenMünchenDeutschland
  3. 3.Munich Cluster for Systems Neurology (SyNergy)MünchenDeutschland
  4. 4.Hertie Institut für Zellbiologie neurologischer ErkrankungenUniversität TübingenTübingenDeutschland
  5. 5.BioMedizinisches ZentrumLudwig-Maximilians-Universität MünchenMünchenDeutschland
  6. 6.Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) MünchenMünchenDeutschland

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