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Epidemiologie und Ursachen der Parkinson-Erkrankung

Epidemiology and causes of Parkinson’s disease

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Zusammenfassung

Die Parkinson-Erkrankung ist die zweithäufigste neurodegenerative Erkrankung, die mit zunehmender Alterung der Industriegesellschaften eine wachsende sozioökonomische Relevanz bekommt. Ein kleiner Teil der unterschiedlichen Erkrankungsformen (<5 %) ist monogen, d. h. durch Mutationen in einzelnen Genen, bedingt. Nach heutigem Stand sind für die klinisch klassische Parkinson-Form drei autosomal-dominant (SNCA, LRRK2, VPS35) und drei autosomal-rezessiv wirkende kausale Gene (Parkin, PINK1, DJ-1) bekannt. Daneben existiert eine Vielzahl von Genen, die für atypische Parkinson-Formen verantwortlich sind. Der idiopathische M. Parkinson hingegen ist multifaktoriell bedingt. Genomweite Assoziationsstudien haben für diese Parkinson-Form insgesamt 26 Genorte etabliert. Für die meisten dieser Genorte sind die der Assoziation zugrunde liegenden funktionellen genetischen Varianten noch nicht identifiziert und die entsprechenden Pathomechanismen noch nicht verstanden. Des Weiteren gibt es eine Reihe mit der idiopathischen Parkinson-Erkrankung assoziierter Umwelt- und Lebensstilfaktoren. Als genuine Risikofaktoren können eine Exposition zu Pestiziden und möglicherweise eine positive Anamnese für Kopftraumata angesehen werden. Andere mit der Parkinson-Erkrankung assoziierte Faktoren wie etwa Rauchen, Kaffee- und Alkoholkonsum stellen möglicherweise keine Risikofaktoren dar; die Ursache-Wirkungs-Beziehung ist für viele der Faktoren noch ungeklärt. Ein Patient mit einer positiven Familienanamnese und/oder einem jungen Erkrankungsalter sollte hinsichtlich einer möglicherweise vorliegenden monogenen Krankheitsform genetisch beraten werden. Eine Krankheitsvorhersage für die idiopathische Erkrankungsform aufgrund genetischer und Umwelt-/Lebensstilfaktoren ist hingegen noch nicht möglich und potenzielle genspezifische Therapien befinden sich noch in Entwicklungs- und ersten Testphasen.

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease and has a growing socioeconomic impact due to demographic changes in the industrial nations. There are several forms of PD, a fraction of which (<5%) are monogenic, i. e. caused by mutations in single genes. At present, six genes have been established for the clinically classical form of parkinsonism including three autosomal dominantly (SNCA, LRRK2, VPS35) and three autosomal recessively inherited ones (Parkin, PINK1, DJ-1). In addition, there are a plethora of genes causing atypical forms of parkinsonism. In contrast, idiopathic PD is of a multifactorial nature. Genome-wide association studies have established a total of 26 genetic loci for this form of the disease; however, for most of these loci the underlying functional genetic variants have not yet been identified and the respective disease mechanisms remain unresolved. Furthermore, there are a number of environmental and life style factors that are associated with idiopathic PD. Exposure to pesticides and possibly a history of head trauma represent genuine risk factors. Other PD-associated factors, such as smoking and intake of coffee and alcohol may not represent risk factors per se and the cause-effect relationship has not yet been elucidated for most of these factors. A patient with a positive family history and/or an early age of disease onset should undergo counseling with respect to a possible monogenic form of the disease. Disease prediction based on genetic, environmental and life style factors is not yet possible for idiopathic PD and potential gene-specific therapies are currently in the development or early testing phase.

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Danksagung

Unser Dank gilt allen Mitarbeitern und Kooperationspartnern, die zur Erstellung und Aktualisierung der PDGene- und MDSGene-Datenbanken beigetragen haben. C.M. Lill erhält Förderungen der International Parkinson and Movement Disorder Society (MDS), der Deutschen Forschungsgemeinschaft (FOR2488/1, GZ LI 2654/2-1), der Possehl-Stiftung, der Renate-Maaß-Stiftung und der Universität zu Lübeck (Mittel der Sektion Medizin, J21-2016). C. Klein wird von der DFG (FOR2488/1), der MDS und der Hermann und Lilly Schilling-Stiftung gefördert.

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  1. Institut für Neurogenetik, Universitätsklinikum Schleswig Holstein, Campus Lübeck, Universität zu Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Deutschland

    C. M. Lill &  C. Klein

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  1. C. M. Lill
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Correspondence to C. Klein.

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C. M. Lill gibt an, dass kein Interessenkonflikt besteht. C. Klein ist als medizinische Beraterin bei Centogene tätig.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Lill, C.M., Klein, C. Epidemiologie und Ursachen der Parkinson-Erkrankung. Nervenarzt 88, 345–355 (2017). https://doi.org/10.1007/s00115-017-0288-0

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