Objective: Our objective was to evaluate phenotype modifying effects of variants in longevity genes in PD.

Background: Parkinson´s disease (PD) has a large phenotypic variability, which may, at least partly, be genetically driven including alterations of gene products. Candidates might not only be proteins associated with disease risk but also pathways that play a role in aging.

Method: We analysed two cohorts, one comprising 524 PD patients who underwent genotyping for the “KL-VS”-variant in Klotho and a second cohort comprising 125 PD patients and 50 control patients (CON) who underwent biochemical CSF analyses of Klotho and the FGF23 protein as well as Vitamin-D-metabolites.

Results: Female PD patients carrying the “KL-VS”-variant demonstrated a shorter interval between PD onset and onset of cognitive impairment. CSF protein levels of Klotho and FGF23 were lower in PD patients irrespective of gender compared to CON. Moreover, low CSF levels of Klotho were associated with higher scores in UPDRS III and HY.

Conclusion: Our results indicate that genetic variants in Klotho along with its corresponding CSF protein profiles are associated with aspects of disease severity in PD. These findings suggest that pathways associated with aging are promising targets for future biomarker research in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-longevity-gene-klotho-and-its-csf-protein-profiles-as-modifier-for-parkinsons-disease-in-a-longitudinal-study/