Journal Article

DZNE-2021-01278

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The longevity gene Klotho and its cerebrospinal fluid protein profiles as a modifier for Parkinson´s disease.

Zimmermann, M. (First author)DZNE* ; Köhler, L. ; Kovarova, M. ; Lerche, S.DZNE* ; Schulte, C.DZNE* ; Wurster, I.DZNE* ; Machetanz, G.DZNE* ; Deuschle, C.DZNE* ; Hauser, A.-K.DZNE* ; Gasser, T.DZNE* ; Berg, D.Extern* ; Schleicher, E. ; Maetzler, W.Extern* ; Brockmann, K. (Last author)DZNE*

2021
Blackwell Science Oxford

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Please use a persistent id in citations: doi:10.1111/ene.14733

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.

Keyword(s): Biomarkers (MeSH) ; Cerebrospinal Fluid Proteins (MeSH) ; Cohort Studies (MeSH) ; Humans (MeSH) ; Longevity (MeSH) ; Mental Status and Dementia Tests (MeSH) ; Parkinson Disease: genetics (MeSH) ; Klotho ; Parkinson´s disease ; aging ; genetic modifier ; longevity genes ; Biomarkers ; Cerebrospinal Fluid Proteins

Note: ISSN 1468-1331 not unique: **2 hits**.

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Contributing Institute(s):

1. Parkinson Genetics (AG Gasser)
2. Core ICRU (Core ICRU)
3. Parkinson's Disease Genetics (AG Berg)
4. Biobanking Facility Tübingen (Biobanking Facility Tübingen)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2021

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Database coverage:
; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Ebsco Academic Search ; IF >= 5 ; JCR ; SCOPUS ; Web of Science Core Collection

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