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Genetik der Demenzen

Genetics of dementia

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Zusammenfassung

Den meisten psychischen Erkrankungen des Erwachsenenalters liegt eine multifaktorielle Verursachung zugrunde. Dies trifft auch für die Demenzerkrankungen zu, wobei es jedoch seltene Erkrankungen bzw. familiäre Unterformen häufiger Demenzerkrankungen gibt, die einem monogenen (mendelischen) Erbgang folgen. Die durch Mutationen in den Genen Präsenilin 1, Präsenilin 2 und Amyloid-Precursor-Protein verursachte Alzheimer-Demenz betrifft in erster Linie Patienten mit Krankheitsbeginn im jüngeren Lebensalter. Bei den frontotemporalen Lobärdegenerationen liegt eine autosomal-dominante Vererbung in rund 10 % der Fälle vor. Die genetische Beratung bei Demenzerkrankungen, die nach den aktuellen S3-Leitlinien der S3-Leitlinien Demenz der Deutschen Gesellschaft für Psychiatrie, Psychotherapie und Nervenheilkunde und der Deutschen Gesellschaft für Neurologie bei Verdacht auf das Vorliegen einer monogen vererbten Demenzerkrankung angeboten werden sollte, muss den Vorgaben des Gendiagnostikgesetzes folgen.

Summary

Most psychiatric diseases in adulthood have a multifactorial origin. This also applies for most cases of dementia; however, rare familial forms of Alzheimer’s disease and frontotemporal lobar degeneration follow an autosomal dominant (Mendelian) inheritance pattern. Alzheimer’s disease that is caused by mutations in the genes for presenilin 1, presenilin 2 and amyloid precursor protein has an onset under the age of 65 years in most cases. Approximately 10 % of frontotemporal lobar degeneration cases display an autosomal dominant inheritance pattern. According to the current S3 guidelines on dementia of the German Association for Psychiatry, Psychotherapy and Psychosomatics and the German Society of Neurology, genetic counseling should be offered if an autosomal dominant disease pattern is suspected. Genetic counseling must conform to the German Genetic Diagnostics Act (Gendiagnostikgesetz).

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Literatur

  1. Slooter AJC et al (1998) Risk estimates of dementia by apolipoprotein E genotypes from a population-based incidence study: the Rotterdam Study. Arch Neurol 55:964–968

    Article  CAS  PubMed  Google Scholar 

  2. Bird TD (o J) Alzheimer disease overview, in GeneReviews® (1996–2014). In: Pagon RA et al (Hrsg) 1993–2015 University of Washington, Seattle University of Washington, Seattle. All rights reserved. Seattle (WA). http://www.ncbi.nlm.nih.gov/books/NBK1161/

  3. WHO (2010) International statistical classification of diseases and related health problems, 10th revision. World Health Organization, Malta

  4. McKhann GM et al (2011) The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7(3):263–269

    Article  PubMed Central  PubMed  Google Scholar 

  5. Cupples LA et al (2004) Estimating risk curves for first-degree relatives of patients with Alzheimer’s disease: the REVEAL study. Genet Med 6(4):192–196

    Article  PubMed  Google Scholar 

  6. Blacker D et al (1997) ApoE-4 and age at onset of Alzheimer’s disease: the NIMH genetics initiative. Neurology 48:139–147

    Article  CAS  PubMed  Google Scholar 

  7. Martins CA et al (2005) APOE alleles predict the rate of cognitive decline in Alzheimer disease: a nonlinear model. Neurology 65(12):1888–1893

    Article  CAS  PubMed  Google Scholar 

  8. Zlokovic BV (2013) Cerebrovascular effects of apolipoprotein E: implications for Alzheimer disease. JAMA Neurol 70(4):440–444

    Article  PubMed Central  PubMed  Google Scholar 

  9. Genin E et al (2011) APOE and Alzheimer disease: a major gene with semi-dominant inheritance. Mol Psychiatry 16(9):903–907

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Bekris LM et al (2010) Genetics of Alzheimer disease. J Geriatr Psychiatry Neurol 23(4):213–227

    Article  PubMed Central  PubMed  Google Scholar 

  11. American College of Medical Genetics/American Society of Human Genetics Working Group on ApoE and Alzheimer disease (1995) Statement on use of apolipoprotein E testing for Alzheimer disease. JAMA 274(20):1627–1679

    Article  Google Scholar 

  12. Tosto G, Reitz C (2013) Genome-wide association studies in Alzheimer’s disease: a review. Curr Neurol Neurosci Rep 13(10):381

    Article  PubMed  Google Scholar 

  13. Farlow JL, Foroud T (2013) The genetics of dementia. Semin Neurol 33(4):417–422

    Article  PubMed Central  PubMed  Google Scholar 

  14. Ryman DC et al (2014) Symptom onset in autosomal dominant Alzheimer disease: a systematic review and meta-analysis. Neurology 83(3):253–260

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Campion D et al (1999) Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum. Am J Hum Genet 65(3):664–670

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Raux G et al (2005) Molecular diagnosis of autosomal dominant early onset Alzheimer’s disease: an update. J Med Genet 42(10):793–795

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Loy CT et al (2014) Genetics of dementia. Lancet 383(9919):828–840

    Article  CAS  PubMed  Google Scholar 

  18. Tanahashi H et al (1996) Sequence analysis of presenilin-1 gene mutation in Japanese Alzheimer’s disease patients. Neurosci Lett 218(2):139–141

    Article  CAS  PubMed  Google Scholar 

  19. Jayadev S et al (2010) Alzheimer’s disease phenotypes and genotypes associated with mutations in presenilin 2. Brain 133(Pt 4):1143–1154

    Article  PubMed Central  PubMed  Google Scholar 

  20. Onyike C, Diehl-Schmid J (2013) The epidemiology of frontotemporal dementia. Int Rev Psychiatry 25(2):130–137

    Article  PubMed Central  PubMed  Google Scholar 

  21. Johnson J et al (2005) Frontotemporal lobar degeneration: demographic characteristics among 353 patients. Arch Neurol 62:925–930

    PubMed  Google Scholar 

  22. Rascovsky K et al (2011) Sensitivity of revised diagnostic criteria for the behavioral variant of frontotemporal dementia. Brain 134:2456–2477

    Article  PubMed Central  PubMed  Google Scholar 

  23. Goldman J et al (2004) Frontotemporal dementia: genetics and genetic counseling dilemmas. Neurologist 10:227–234

    Article  PubMed  Google Scholar 

  24. Hodges J et al (2010) Semantic dementia: demography, familial factors and survival in a consecutive series of 100 cases. Brain 133:300–306

    Article  PubMed  Google Scholar 

  25. Ferrari R et al (2014) Frontotemporal dementia and its subtypes: a genome-wide association study. Lancet Neurol 13(7):686–699

    Article  PubMed Central  PubMed  Google Scholar 

  26. Sieben A et al (2012) The genetics and neuropathology of frontotemporal lobar degeneration. Acta Neuropathol 12:353–372

    Article  Google Scholar 

  27. DeJesus-Hernandez M et al (2011) Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72(2):245–256

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Fong JC, Karydas AM, Goldman JS (2012) Genetic counseling for FTD/ALS caused by the C9ORF72 hexanucleotide expansion. Alzheimers Res Ther 4(4):27

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Landqvist Waldo M et al (2013) Frontotemporal dementia with a C9ORF72 expansion in a Swedish family: clinical and neuropathological characteristics. Am J Neurodegener Dis 2(4):276–286

    Google Scholar 

  30. Bieniek KF et al (2014) Expanded C9ORF72 hexanucleotide repeat in depressive pseudodementia. JAMA Neurol 71(6):775–781

    Article  PubMed Central  PubMed  Google Scholar 

  31. S3-Leitlinie „Demenzen“ 23. November 2009, S3-Leitlinie 038/013

  32. Goldman JS (2012) New approaches to genetic counseling and testing for Alzheimer’s disease and frontotemporal degeneration. Curr Neurol Neurosci Rep 12(5):502–510

    Article  PubMed Central  PubMed  Google Scholar 

  33. Diehl-Schmid J (2013) Frontotemporale lobäre Degenerationen. Erste Symptome unspezifisch – im Frühstadium häufig nicht erkannt. NeuroTransmitter 7–8:46–53

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Einhaltung ethischer Richtlinien

Interessenkonflikt. J. Diehl-Schmid und K. Oexle geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Authors and Affiliations

  1. Klinik und Poliklinik für Psychiatrie und Psychotherapie, TU München, Ismaninger Str. 22, 81675, München, Deutschland

    J. Diehl-Schmid

  2. Institut für Humangenetik, TU München, München, Deutschland

    K. Oexle

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Correspondence to J. Diehl-Schmid.

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Diehl-Schmid, J., Oexle, K. Genetik der Demenzen. Nervenarzt 86, 891–902 (2015). https://doi.org/10.1007/s00115-015-4276-y

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  • DOI: https://doi.org/10.1007/s00115-015-4276-y

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