{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:53:51Z","timestamp":1787496831903,"version":"build-2736575974"},"reference-count":98,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T00:00:00Z","timestamp":1649980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Alterations in the sphingolipid metabolism of Parkinson\u2019s Disease (PD) could be a potential diagnostic feature. Only around 10\u201315% of PD cases can be diagnosed through genetic alterations, while the remaining population, idiopathic PD (iPD), manifest without validated and specific biomarkers either before or after motor symptoms appear. Therefore, clinical diagnosis is reliant on the skills of the clinician, which can lead to misdiagnosis. IPD cases present with a spectrum of non-specific symptoms (e.g., constipation and loss of the sense of smell) that can occur up to 20 years before motor function loss (prodromal stage) and formal clinical diagnosis. Prodromal alterations in metabolites and proteins from the pathways underlying these symptoms could act as biomarkers if they could be differentiated from the broad values seen in a healthy age-matched control population. Additionally, these shifts in metabolites could be integrated with other emerging biomarkers\/diagnostic tests to give a PD-specific signature. Here we provide an up-to-date review of the diagnostic value of the alterations in sphingolipids pathway in PD by focusing on the changes in definitive PD (postmortem confirmed brain data) and their representation in \u201cprobable PD\u201d cerebrospinal fluid (CSF) and blood. We conclude that the trend of holistic changes in the sphingolipid pathway in the PD brain seems partly consistent in CSF and blood, and could be one of the most promising pathways in differentiating PD cases from healthy controls, with the potential to improve early-stage iPD diagnosis and distinguish iPD from other Parkinsonism when combined with other pathological markers.<\/jats:p>","DOI":"10.3390\/cells11081353","type":"journal-article","created":{"date-parts":[[2022,4,16]],"date-time":"2022-04-16T07:42:41Z","timestamp":1650094961000},"page":"1353","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Clinical Sphingolipids Pathway in Parkinson\u2019s Disease: From GCase to Integrated-Biomarker Discovery"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0122-3575","authenticated-orcid":false,"given":"Ali","family":"Esfandiary","sequence":"first","affiliation":[{"name":"Drug Delivery, Disposition and Dynamics, Monash University, Parkville, VIC 3052, Australia"},{"name":"Melbourne Centre for Nanofabrication, Victorian Node of the Australian National Fabrication Facility, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8167-4917","authenticated-orcid":false,"given":"David Isaac","family":"Finkelstein","sequence":"additional","affiliation":[{"name":"Howard Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas Hans","family":"Voelcker","sequence":"additional","affiliation":[{"name":"Drug Delivery, Disposition and Dynamics, Monash University, Parkville, VIC 3052, Australia"},{"name":"Melbourne Centre for Nanofabrication, Victorian Node of the Australian National Fabrication Facility, Clayton, VIC 3168, Australia"},{"name":"Commonwealth Scientific and Industrial Research Organization (CSIRO), Clayton, VIC 3168, Australia"},{"name":"Materials Science and Engineering, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3104-309X","authenticated-orcid":false,"given":"David","family":"Rudd","sequence":"additional","affiliation":[{"name":"Drug Delivery, Disposition and Dynamics, Monash University, Parkville, VIC 3052, Australia"},{"name":"Melbourne Centre for Nanofabrication, Victorian Node of the Australian National Fabrication Facility, Clayton, VIC 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S1474-4422(21)00030-2","article-title":"Challenges in the diagnosis of Parkinson\u2019s disease","volume":"20","author":"Tolosa","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1002\/mds.26424","article-title":"MDS clinical diagnostic criteria for Parkinson\u2019s disease","volume":"30","author":"Postuma","year":"2015","journal-title":"Mov. 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