The longevity gene <i>Klotho</i> and its cerebrospinal fluid protein profiles as a modifier for Parkinson´s disease

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 proteins associated with risk but also pathways that play role in aging. Objective To evaluate phenotype-modifying effects genetic variants Klotho, longevity gene. Methods We analyzed two longitudinal cohorts: one local cohort comprising 459 PD patients who underwent genotyping for the KL-VS haplotype Klotho subgroup 125 and 50 healthy controls biochemical cerebrospinal fluid (CSF) analyses fibroblast growth factor 23 as well vitamin D metabolites. The second comprised 297 from Parkinsonʼs Progression Markers Initiative (PPMI) validation genetic−clinical findings. Results carrying demonstrated shorter interval between onset cognitive impairment (both cohorts) higher Unified Disease Rating Scale part III (UPDRS III) scores (PPMI). CSF protein levels were lower irrespective gender compared to controls. Moreover, low UPDRS Hoehn Yahr Scale. Conclusions Our results indicate together its corresponding profiles are aspects severity PD. These findings suggest aging targets future biomarker research