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@ARTICLE{Zimmermann:157821,
      author       = {Zimmermann, Milan and Köhler, Leonie and Kovarova, Marketa
                      and Lerche, Stefanie and Schulte, Claudia and Wurster,
                      Isabel and Machetanz, Gerrit and Deuschle, Christian and
                      Hauser, Ann-Kathrin and Gasser, Thomas and Berg, Daniela and
                      Schleicher, Erwin and Maetzler, Walter and Brockmann,
                      Kathrin},
      title        = {{T}he longevity gene {K}lotho and its cerebrospinal fluid
                      protein profiles as a modifier for {P}arkinson´s disease.},
      journal      = {European journal of neurology},
      volume       = {28},
      number       = {5},
      issn         = {1351-5101},
      address      = {Oxford},
      publisher    = {Blackwell Science},
      reportid     = {DZNE-2021-01278},
      pages        = {1557-1565},
      year         = {2021},
      note         = {ISSN 1468-1331 not unique: **2 hits**.},
      abstract     = {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.},
      keywords     = {Biomarkers / Cerebrospinal Fluid Proteins / Cohort Studies
                      / Humans / Longevity / Mental Status and Dementia Tests /
                      Parkinson Disease: genetics / Klotho (Other) / Parkinson´s
                      disease (Other) / aging (Other) / genetic modifier (Other) /
                      longevity genes (Other) / Biomarkers (NLM Chemicals) /
                      Cerebrospinal Fluid Proteins (NLM Chemicals)},
      cin          = {AG Gasser / Core ICRU / AG Berg / Biobanking Facility
                      Tübingen},
      ddc          = {610},
      cid          = {I:(DE-2719)1210000 / I:(DE-2719)1240005 /
                      I:(DE-2719)5000055 / I:(DE-2719)1240004},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33449400},
      doi          = {10.1111/ene.14733},
      url          = {https://pub.dzne.de/record/157821},
}