Parkinson Genetics

• Analysis of genetic factors in sporadic and familial Parkinson’s disease
• Leucine-rich repeat kinase 2, LRRK2 (Park8)
• Staff

Parkinson's disease (PD) is the second most common neurodegenerative disease with an increasing prevalence due to the demographic development of Western societies. The vast majority of patients develop the disease sporadically (95%), meaning that there is no evident familial pattern of inheritance. Despite the rareness of monogenic forms of PD (5%) the identification and functional analysis of these genes and their gene products contributed greatly to the elucidation of cellular mechanisms and networks involved in the pathogenesis of PD. Nevertheless, causative factors for the more common but probably very heterogeneous forms of sporadic PD are not known to date. There is accumulating evidence that genetic factors might also contribute to sporadic PD probably by influencing disease susceptibility and/ or age at disease onset. Those genes in which mutations lead to familial PD are also potential candidates for an involvement in sporadic PD. One of these genes is the gene SNCA, encoding the protein α-synuclein. Three point mutations as well as tri- and duplications of genetic loci encompassing wild-type α-synuclein cause hereditary autosomal-dominant PD. Therefore, increased levels of otherwise normal α-synuclein is responsible for the development of PD in these families.

It has been hypothesized that genetic variability of the α-synuclein gene could also play an important role in the pathogenesis of sporadic PD. This is suggested by the fact that α-synuclein is the major component of intracellular aggregates, called Lewy bodies, typically observed in sporadic PD. Funded by the German National Genome Research Network (NGFN) and in cooperation with the Helmholtz-Center in Munich we could identify an association between variants in the 3' region of the α-synuclein gene and the risk for sporadic PD in a comprehensive association analysis using modern high-throughput genotyping techniques .

This finding has recently been convincingly confirmed by a genome wide association study (GWAS) conducted in cooperation with a group at the National Institutes of Health (NIH).

Contact: Prof. Dr. T. Gasser

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