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Postmortale Diagnosestellung bei Morbus Alzheimer

Stadiengliederungen der kennzeichnenden Hirnveränderungen

Post-mortem diagnosis of Alzheimer’s disease

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Zusammenfassung

Der Morbus Alzheimer ist eine langsam, jedoch stetig und unaufhaltsam voranschreitende neurodegenerative Erkrankung des menschlichen Zentralnervensystems, die etwa 15% aller über 65-Jährigen betrifft. Im Verlauf der Erkrankung entstehen sowohl intraneuronale als auch extrazelluläre Ablagerungen pathologisch veränderter Proteine. Die intraneuronalen Aggregate bestehen überwiegend aus abnormem tau(τ)-Protein. Sie führen zur Bildung von neurofibrillären Veränderungen in den Perikaryen und von Neuropilfäden in Zellfortsätzen betroffener Neurone. Die Entwicklung der extrazellulären Amyloid-β(Aβ)-Ablagerungen und der intraneuronalen τ-Aggregate vollzieht sich in langsam voranschreitenden Prozessen. Innerhalb der Hirnrinde beginnt die Ablagerung von Aβ im Neokortex, während die ersten neurofibrillären Veränderungen in den allokortikalen Nervenzellen der Regio transentorhinalis zu finden sind. Von hier ausgehend expandieren beide Veränderungen in immer weitere Felder und Regionen. Diese Ausbreitung erlaubt eine Gliederung der pathologischen Veränderungen in Stadien bzw. Phasen, entsprechend dem zunehmenden Schweregrad des klinischen Bildes. Nach dieser Einteilung kann beurteilt werden, inwieweit ein demenzielles Krankheitsbild durch den Morbus Alzheimer verursacht ist.

Summary

Alzheimer’s disease is a slowly but continuously progressive degenerative disorder of the human central nervous system seen in ~15% of elderly people over the age of 65 years. Morphological hallmarks of this process are intra- and extracellular protein aggregates. The intraneuronal protein aggregates are primarily made up of abnormal phosphorylated τ-protein, which builds neurofibrillary tangles, neuropil threads and dystrophic neurites in neuritic plaques. The extracellular deposits consist of amyloid β-protein (Aβ) aggregates showing the characteristics of amyloid fibrils. The evolution of neurofibrillary changes as well as Aβ-deposition in brain regions follows a distinct hierarchical sequence spanning many decades. Aβ deposition begins in the neocortex whereas neurofibrillary pathology starts in the allocortical nerve cells of the transentorhinal region. Both transformations continue to increase in severity and expand into further areas and regions. The hierarchical pattern allows an easily understandable staging of neurofibrillary and Aβ pathology which in turn reflects the clinical gravity of the disease. According to these stages a dementing disorder can be diagnostically attributed to Alzheimer’s disease.

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Danksagung

Diese Arbeit entstand mit dankenswerter Unterstützung durch die Deutsche Forschungsgemeinschaft, des Bundesministeriums für Forschung, Bildung und Technologie und der BONFOR-Forschungsförderung der Universität Bonn. Der besondere Dank der Autoren gebührt Frau I. Szasz und Herrn U. Klatt für die Anfertigung der Graphiken und der phototechnischen Arbeiten.

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  1. Institut für Neuropathologie, Medizinische Einrichtungen der Universität Bonn

    D. R. Thal

  2. Institut für Klinische Neuroanatomie, Johann Wolfgang Goethe Universität Frankfurt am Main

    H. Braak

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  1. D. R. Thal
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  2. H. Braak
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Thal, D.R., Braak, H. Postmortale Diagnosestellung bei Morbus Alzheimer. Pathologe 26, 201–213 (2005). https://doi.org/10.1007/s00292-004-0695-4

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