{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T16:41:56Z","timestamp":1786466516647,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011736","name":"Ministerium f\u00fcr Wirtschaft, Arbeit und Wohnungsbau Baden-W\u00fcrttemberg","doi-asserted-by":"publisher","award":["FKZ AZ 35\u20104223.10\/8"],"award-info":[{"award-number":["FKZ AZ 35\u20104223.10\/8"]}],"id":[{"id":"10.13039\/501100011736","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":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Parkinson's disease (PD) is an age\u2010related condition characterized by substantial phenotypic variability. Consequently, pathways and proteins involved in biological aging, such as the central aging pathway comprising insulin\u2010like growth factor 1\u2013\u03b1\u2010Klotho\u2013sirtuin 1\u2013forkhead box O3\u2013peroxisome proliferator\u2010activated receptor \u03b3, may potentially influence disease progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cerebrospinal fluid (CSF) levels of \u03b1\u2010Klotho in 471 PD patients were examined. Of the 471 patients, 96 carried a <jats:italic>GBA1<\/jats:italic> variant (PD <jats:italic>GBA1<\/jats:italic>), whilst the 375 non\u2010carriers were classified as PD wild\u2010type (PD WT). Each patient was stratified into a CSF \u03b1\u2010Klotho tertile group based on the individual level. Kaplan\u2013Meier survival curves and Cox regression analysis stratified by tertile groups were conducted. These longitudinal data were available for 255 patients. Follow\u2010up times reached from 8.4 to 12.4\u2009years. The stratification into PD WT and PD <jats:italic>GBA1<\/jats:italic> was undertaken to evaluate potential continuum patterns, particularly in relation to CSF levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Higher CSF levels of \u03b1\u2010Klotho were associated with a significant later onset of cognitive impairment. Elevated levels of \u03b1\u2010Klotho in CSF were linked to higher Montreal Cognitive Assessment scores in male PD patients with <jats:italic>GBA1<\/jats:italic> mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results indicate that higher CSF levels of \u03b1\u2010Klotho are associated with a delayed cognitive decline in PD. Notably, this correlation is more prominently observed in PD patients with <jats:italic>GBA1<\/jats:italic> mutations, potentially reflecting the accelerated biological aging profile characteristic of individuals harboring <jats:italic>GBA1<\/jats:italic> variants.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.16388","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T09:29:28Z","timestamp":1719826168000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Association of elevated cerebrospinal fluid levels of the longevity protein \u03b1\u2010Klotho with a delayed onset of cognitive impairment in Parkinson's disease patients"],"prefix":"10.1111","volume":"31","author":[{"given":"Milan","family":"Zimmermann","sequence":"first","affiliation":[{"name":"Center of Neurology Department of Neurodegeneration and Hertie\u2010Institute for Clinical Brain Research University of Tuebingen  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