Die Genetik des Lipidstoffwechsels als Risikofaktor für kognitive Defizite bei der Parkinson-Krankheit

Die Parkinson-Krankheit gehört zu den Basalganglienerkrankungen und ist nach der Alzheimer-Krankheit die zweithäufigste neurodegenerative Erkrankung. Von den typischen motorischen Leitsymptomen sind kognitive Defizite, auch Parkinson-Demenz genannt, abzugrenzen. Etwa 75% der Parkinson-Syndrome sind...

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Bibliographic Details
Main Author: Söling, Charlotte
Contributors: Dodel, Richard (Prof. Dr. med.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2020
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Parkinson’s Disease is the second most neurodegenerative disorder following Alzheimer’s Disease. Among Patients with Parkinson’s Disease cognitive decline is common and occurs after motor symptoms. The cause of Parkinson’s Disease Dementia is not understood so far. Therefore, analyzing genetic risk factors is important for identifying individuals at high risk of Parkinson’s Disease Dementia. Cholesterol metabolism and its regulation play a major role in an operating central nervous system. Apolipoproteins are associated with a diagnosis of cognitive impairment in Alzheimer’s Disease and might influence a cognitive decline among Parkinson’s patients as well. In this dissertation a total of 94 patients with Parkinson’s Disease (47 patients without cognitive impairment, 47 patients with dementia) were included from an observational German multicenter cohort study (LANDSCAPE study). Primarily, a data matching was held to achieve a higher comparability and a better selection of controls. As criteria served gender, a period of disease ≥ 6 years and a difference of age ± 7 years. Several studies reported of different genes as being associated with the risk of developing Parkinson’s Disease Dementia. To further characterize this association sequencing of the coding region of the Apolipoproteins E, A1 and J and of selected exons of Adenosine Triphosphate-binding Cassette Transporter A1 and Very-Low-Density-Lipoprotein Receptor was performed. A total of 8 variants were found in both cases and controls. No significant differences were observed in the distribution of these Single Nucleotide Polymorphisms between Parkinson’s Disease Dementia patients and controls. Nonetheless, regarding the present results rs7982 (Apolipoprotein J Exon 5; Odds ratio 1.575; 95% confidence interval=0.680~3.646; p=0.288) and rs2066714/ rs4149313 (Adenosine Triphosphate-binding Cassette Transporter A1 Exon 18; Odds Ratio 1.4; 95% confidence interval=0.551~3.554; p=0.478) have been suggested to be risk factors for dementia in Parkinson’s Disease. The lack of significance might be based on the small number of cases. As a perspective more patients of the LANDSCAPE collective could be included and investigated concerning these 2 variants as above-mentioned.