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000157821 1001_ $$0P:(DE-2719)9000951$$aZimmermann, Milan$$b0$$eFirst author$$udzne
000157821 245__ $$aThe longevity gene Klotho and its cerebrospinal fluid protein profiles as a modifier for Parkinson´s disease.
000157821 260__ $$aOxford$$bBlackwell Science$$c2021
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000157821 520__ $$aParkinson´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.
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000157821 542__ $$2Crossref$$i2021-02-06$$uhttp://creativecommons.org/licenses/by-nc/4.0/
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000157821 650_7 $$2Other$$a Klotho 
000157821 650_7 $$2Other$$aParkinson´s disease
000157821 650_7 $$2Other$$aaging
000157821 650_7 $$2Other$$agenetic modifier
000157821 650_7 $$2Other$$alongevity genes
000157821 650_7 $$2NLM Chemicals$$aBiomarkers
000157821 650_7 $$2NLM Chemicals$$aCerebrospinal Fluid Proteins
000157821 650_2 $$2MeSH$$aBiomarkers
000157821 650_2 $$2MeSH$$aCerebrospinal Fluid Proteins
000157821 650_2 $$2MeSH$$aCohort Studies
000157821 650_2 $$2MeSH$$aHumans
000157821 650_2 $$2MeSH$$aLongevity
000157821 650_2 $$2MeSH$$aMental Status and Dementia Tests
000157821 650_2 $$2MeSH$$aParkinson Disease: genetics
000157821 7001_ $$aKöhler, Leonie$$b1
000157821 7001_ $$aKovarova, Marketa$$b2
000157821 7001_ $$0P:(DE-2719)2812186$$aLerche, Stefanie$$b3$$udzne
000157821 7001_ $$0P:(DE-2719)9000366$$aSchulte, Claudia$$b4$$udzne
000157821 7001_ $$0P:(DE-2719)2812736$$aWurster, Isabel$$b5$$udzne
000157821 7001_ $$0P:(DE-2719)9000193$$aMachetanz, Gerrit$$b6$$udzne
000157821 7001_ $$0P:(DE-2719)2812432$$aDeuschle, Christian$$b7$$udzne
000157821 7001_ $$0P:(DE-2719)2351249$$aHauser, Ann-Kathrin$$b8$$udzne
000157821 7001_ $$0P:(DE-2719)2320009$$aGasser, Thomas$$b9$$udzne
000157821 7001_ $$0P:(DE-2719)2000059$$aBerg, Daniela$$b10$$udzne
000157821 7001_ $$aSchleicher, Erwin$$b11
000157821 7001_ $$0P:(DE-2719)2810915$$aMaetzler, Walter$$b12$$udzne
000157821 7001_ $$0P:(DE-2719)2811916$$aBrockmann, Kathrin$$b13$$eLast author$$udzne
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