TY  - JOUR
AU  - Zimmermann, Milan
AU  - Köhler, Leonie
AU  - Kovarova, Marketa
AU  - Lerche, Stefanie
AU  - Schulte, Claudia
AU  - Wurster, Isabel
AU  - Machetanz, Gerrit
AU  - Deuschle, Christian
AU  - Hauser, Ann-Kathrin
AU  - Gasser, Thomas
AU  - Berg, Daniela
AU  - Schleicher, Erwin
AU  - Maetzler, Walter
AU  - Brockmann, Kathrin
TI  - The longevity gene Klotho and its cerebrospinal fluid protein profiles as a modifier for Parkinson´s disease.
JO  - European journal of neurology
VL  - 28
IS  - 5
SN  - 1351-5101
CY  - Oxford
PB  - Blackwell Science
M1  - DZNE-2021-01278
SP  - 1557-1565
PY  - 2021
N1  - ISSN 1468-1331 not unique: **2 hits**.
AB  - 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.To evaluate phenotype-modifying effects of genetic variants in Klotho, a longevity gene.We analyzed two longitudinal cohorts: one local cohort comprising 459 PD patients who underwent genotyping for the KL-VS haplotype in Klotho including a subgroup of 125 PD patients and 50 healthy controls who underwent biochemical cerebrospinal fluid (CSF) analyses of Klotho and fibroblast growth factor 23 as well as vitamin D metabolites. The second cohort comprised 297 patients from the Parkinson's Progression Markers Initiative (PPMI) for validation of genetic-clinical findings.PD patients carrying the KL-VS haplotype demonstrated a shorter interval between PD onset and onset of cognitive impairment (both cohorts) and higher Unified Parkinson´s Disease Rating Scale part III (UPDRS III) scores (PPMI). CSF protein levels of Klotho and fibroblast growth factor 23 were lower in PD patients irrespective of gender compared to controls. Moreover, low CSF levels of Klotho were associated with higher scores in the UPDRS III and Hoehn and Yahr Scale.Our results indicate that genetic variants in Klotho together with its corresponding CSF protein profiles are associated with aspects of disease severity in PD. These findings suggest that pathways associated with aging might be targets for future biomarker research in PD.
KW  - Biomarkers
KW  - Cerebrospinal Fluid Proteins
KW  - Cohort Studies
KW  - Humans
KW  - Longevity
KW  - Mental Status and Dementia Tests
KW  - Parkinson Disease: genetics
KW  -  Klotho  (Other)
KW  - Parkinson´s disease (Other)
KW  - aging (Other)
KW  - genetic modifier (Other)
KW  - longevity genes (Other)
KW  - Biomarkers (NLM Chemicals)
KW  - Cerebrospinal Fluid Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:33449400
DO  - DOI:10.1111/ene.14733
UR  - https://pub.dzne.de/record/157821
ER  -