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Familiäre Alzheimer-Variante mit Amyloidangiopathie als Ausdruck einer APP-Gen-Duplikation

Hereditary Alzheimer’s disease with amyloid angiopathy caused by amyloid precursor protein locus

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Zusammenfassung

Wir berichten über einen Patienten mit einer autosomal-dominant vererbten Demenz. Die Liquordiagnostik zeigte eine Alzheimer-typische Konstellation mit einem erhöhten τ-Protein und erniedrigter Amyloid β 42:40-Ratio. Die MRT des Schädels zeigte vaskuläre Läsionen der weißen Substanz und flächige Demyelinisierungen um die Hinterhörner bei insgesamt mäßiger Hirnatrophie. In der suszeptibilitätsgewichteten Bildgebung (SWI) zeigten sich multiple kleine Hämorrhagien bzw. Hämosiderinablagerungen. Die Genanalyse erbrachte als Ursache eine Duplikation im APP-Gen („amyloid precursor protein“). Bemerkenswert ist das Zusammentreffen von Alzheimer-typischen Liquorveränderungen und bildmorphologischen Zeichen der Amyloidangiopathie, die für die seltene Duplikation des APP-Gens beschrieben sind und bei positiver Familienanamnese Anlass zur erweiterten Genanalyse geben sollten.

Summary

We report a patient with early-onset autosomal dominant dementia. The CSF showed increased levels of tau protein and decreased amyloid beta (ratio 42:40) typical for Alzheimer’s disease. Cerebral MRI revealed vascular lesions and white-matter changes around the posterior horns of the ventricles with only moderate atrophy of the brain. Susceptibility-weighted imaging detected multiple small hemorrhagic changes. Gene analysis revealed amyloid precursor protein (APP) locus duplication as the cause of hereditary Alzheimer’s dementia. The co-occurrence of CSF changes typical for Alzheimer’s disease and MRI findings of cerebral amyloid angiopathy is remarkable, as it is also described for APP locus duplication. In conjunction with a family history suggestive of hereditary dementia, such a constellation should lead to enhanced gene analysis.

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Authors and Affiliations

  1. Klinik für Psychiatrie und Psychotherapie, Friedrich-Schiller-Universität, Jena, Deutschland

    H. Axer, S. Hüge, M. Axer, H. Sauer & K.-J. Bär

  2. Klinik für Neurologie, Friedrich-Schiller-Universität, Erlanger Allee 101, 07747, Jena, Deutschland

    H. Axer & A. Kunze

  3. Praxis für Humangenetik, Freiburg, Deutschland

    C. Wilhelm & J. Kohlhase

  4. Arbeitsbereich Medizinische Physik, Institut für Diagnostische und Interventionelle Radiologie, Friedrich-Schiller-Universität, Jena, Deutschland

    J.R. Reichenbach

  5. Klinik für Nuklearmedizin, Friedrich-Schiller-Universität, Jena, Deutschland

    M. Freesmeyer

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  1. H. Axer
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  2. S. Hüge
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  3. C. Wilhelm
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  4. M. Axer
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  5. A. Kunze
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  6. J.R. Reichenbach
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  7. M. Freesmeyer
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  8. J. Kohlhase
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  9. H. Sauer
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  10. K.-J. Bär
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Correspondence to H. Axer.

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Axer, H., Hüge, S., Wilhelm, C. et al. Familiäre Alzheimer-Variante mit Amyloidangiopathie als Ausdruck einer APP-Gen-Duplikation. Nervenarzt 80, 62–67 (2009). https://doi.org/10.1007/s00115-008-2565-4

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  • DOI: https://doi.org/10.1007/s00115-008-2565-4

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