{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T06:02:41Z","timestamp":1778133761165,"version":"3.51.4"},"reference-count":29,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,2,6]],"date-time":"2021-02-06T00:00:00Z","timestamp":1612569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Parkinson\u00b4s 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate phenotype\u2010modifying effects of genetic variants in <jats:italic>Klotho<\/jats:italic>, a longevity gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed two longitudinal cohorts: one local cohort comprising 459 PD patients who underwent genotyping for the KL\u2010VS haplotype in <jats:italic>Klotho<\/jats:italic> 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\u02bcs Progression Markers Initiative (PPMI) for validation of genetic\u2212clinical findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PD patients carrying the KL\u2010VS haplotype demonstrated a shorter interval between PD onset and onset of cognitive impairment (both cohorts) and higher Unified Parkinson\u00b4s 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results indicate that genetic variants in <jats:italic>Klotho<\/jats:italic> 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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.14733","type":"journal-article","created":{"date-parts":[[2021,1,16]],"date-time":"2021-01-16T00:13:30Z","timestamp":1610756010000},"page":"1557-1565","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["The longevity gene <i>Klotho<\/i> and its cerebrospinal fluid protein profiles as a modifier for Parkinson\u00b4s disease"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7066-7749","authenticated-orcid":false,"given":"Milan","family":"Zimmermann","sequence":"first","affiliation":[{"name":"Center of Neurology Department of Neurodegeneration and Hertie\u2010Institute for Clinical Brain Research University of Tuebingen Tuebingen Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE University of Tuebingen Tuebingen 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