001     157821
005     20240722121853.0
024 7 _ |a 10.1111/ene.14733
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024 7 _ |a pmid:33449400
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024 7 _ |a 1351-5101
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024 7 _ |a 1468-1331
|2 ISSN
024 7 _ |a 1471-0552
|2 ISSN
024 7 _ |a altmetric:97849728
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037 _ _ |a DZNE-2021-01278
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Zimmermann, Milan
|0 P:(DE-2719)9000951
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245 _ _ |a The longevity gene Klotho and its cerebrospinal fluid protein profiles as a modifier for Parkinson´s disease.
260 _ _ |a Oxford
|c 2021
|b Blackwell Science
336 7 _ |a article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a 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.
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542 _ _ |i 2021-02-06
|2 Crossref
|u http://creativecommons.org/licenses/by-nc/4.0/
542 _ _ |i 2021-02-06
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650 _ 7 |a Klotho
|2 Other
650 _ 7 |a Parkinson´s disease
|2 Other
650 _ 7 |a aging
|2 Other
650 _ 7 |a genetic modifier
|2 Other
650 _ 7 |a longevity genes
|2 Other
650 _ 7 |a Biomarkers
|2 NLM Chemicals
650 _ 7 |a Cerebrospinal Fluid Proteins
|2 NLM Chemicals
650 _ 2 |a Biomarkers
|2 MeSH
650 _ 2 |a Cerebrospinal Fluid Proteins
|2 MeSH
650 _ 2 |a Cohort Studies
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Longevity
|2 MeSH
650 _ 2 |a Mental Status and Dementia Tests
|2 MeSH
650 _ 2 |a Parkinson Disease: genetics
|2 MeSH
700 1 _ |a Köhler, Leonie
|b 1
700 1 _ |a Kovarova, Marketa
|b 2
700 1 _ |a Lerche, Stefanie
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700 1 _ |a Schulte, Claudia
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700 1 _ |a Wurster, Isabel
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700 1 _ |a Machetanz, Gerrit
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700 1 _ |a Deuschle, Christian
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700 1 _ |a Hauser, Ann-Kathrin
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700 1 _ |a Gasser, Thomas
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700 1 _ |a Berg, Daniela
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700 1 _ |a Schleicher, Erwin
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700 1 _ |a Maetzler, Walter
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700 1 _ |a Brockmann, Kathrin
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773 1 8 |a 10.1111/ene.14733
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|t European Journal of Neurology
|v 28
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|x 1351-5101
773 _ _ |a 10.1111/ene.14733
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Marc 21