Der Nervenarzt

, Volume 84, Issue 6, pp 732–737 | Cite as

Vaskuläre Faktoren in der Pathogenese der Alzheimer-Krankheit

Aktuelles aus Diagnostik und Therapie

Zusammenfassung

Nach der „Amyloidhypothese“ der Alzheimer-Krankheit (AK) spielt das Amyloid-β(Aβ)-Peptid als primär neurotoxisches Agens eine Schlüsselrolle in der Pathogenese. Eine Vielzahl neuerer Befunde weist jedoch auch auf die Bedeutung einer frühen zerebrovaskulären Dysfunktion zumindest für die sporadische AK als häufigste Form hin. Bereits im präklinischen Verlauf kommt es nicht nur zu neuronalen, sondern auch zu vaskulären Schäden. Zerebrale Minderperfusion, Blut-Hirn-Schranken-Störung und vaskulärer oxidativer Stress sind typische Kennzeichen dieses Erkrankungsstadiums. Besonders bedeutsam ist, dass diese Veränderungen noch vor den klassischen pathologischen Merkmalen wie extrazelluläre Amyloidablagerungen im Hirnparenchym bzw. intrazellulärer Bildung neurofibrillärer Bündel auftreten. Der vorliegende Artikel bietet eine Übersicht über neuere epidemiologische, klinisch-pathologische und experimentelle Belege für ein integratives vaskulär-neuronales Entstehungsmodell der sporadischen AK.

Schlüsselwörter

Alzheimer-Krankheit Vaskuläre Risikofaktoren Neurovaskuläre Einheit Amyloid β Oxidativer Stress 

Vascular factors in the pathogenesis of Alzheimer’s disease

Summary

According to the amyloid hypothesis of Alzheimer’s disease (AD), the amyloid β (Aβ) peptide, as the primary neurotoxic species, plays a key role in the pathogenesis of the disease. However, many lines of recent evidence also point towards a major importance of early cerebrovascular dysfunction at least for the most common form of the disease, sporadic AD. In the preclinical course not only neuronal but also vascular damage frequently occurs. Cerebral hypoperfusion, blood-brain barrier dysfunction and vascular oxidative stress are typical features of this stage of the disease. Most importantly, such alterations precede the classical pathological hallmarks, such as parenchymal deposition of extracellular amyloid and intracellular neurofibrillary tangles. In this article recent epidemiological, clinical pathological and experimental evidence for an integrative vascular neuronal pathogenetic model of sporadic AD is reviewed.

Keywords

Alzheimer’s disease Vascular risk factors Neurovascular unit Amyloid beta Oxidative stress 

Notes

Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehungen hin: Der Autor erhielt Vortragshonorare von Lilly Deutschland GmbH und Servier Deutschland sowie Studienunterstützung von Pfizer und Bristol-Myers Squibb.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Klinik und Poliklinik für Psychiatrie und Psychotherapie, Medizinische FakultätLVR-Klinikum Düsseldorf, Heinrich-Heine-UniversitätDüsseldorfDeutschland

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