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We explored different pathophysiologic mechanisms underlying PD in patients of different ages independently from disease duration, through CSF biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with clinically established diagnosis of PD underwent clinical evaluation through validated clinical scales (MDS-UPDRS, NMSS, MoCA, WOQ, QUIP, UDysRS). CSF inflammatory (YKL-40, TREM-2) and neurodegeneration (A-Beta42 and 40, t-Tau, p-Tau, NfL, Neurogranin, alpha-synuclein) biomarkers were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>95 PD patients were recruited, among whom 43 were younger than 66\u00a0years old, and 52 older. Age strongly correlated with neurofilament CSF levels, both light and heavy chain, with YKL-40 and with tau species. Younger and older patients showed different biomarker profiles. Younger patients showed significantly lower levels of inflammatory molecules (YKL-40), of degeneration biomarkers (tau species, neurofilament light and heavy chains), independently from disease duration. Clinically, younger patients had better scores at MDS-UPDRS parts I and III and were more prone to develop motor fluctuations and impulse control disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data support the hypothesis that PD has different underlying biological features in younger and older subjects. Older subjects may have a broader spectrum of disease mechanisms, reflected in the higher prevalence of amyloid pathology and neurodegeneration, which could underlie the worse cognitive performances and lower dyskinesia burden. They could therefore necessitate a wider array of treatment strategies along with dopaminergic supplementation. Consequently, some of these biomarkers hold promise in refining treatment approaches in PD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-025-13384-7","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T13:53:11Z","timestamp":1758721991000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effect of aging on biomarkers and clinical profile in Parkinson\u2019s disease"],"prefix":"10.1007","volume":"272","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2413-1788","authenticated-orcid":false,"given":"Giulia","family":"Di Lazzaro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Paolini Paoletti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Bellomo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Schirinzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piergiorgio","family":"Grillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido Maria","family":"Giuffr\u00e8","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Petracca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Picca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola Biagio","family":"Mercuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucilla","family":"Parnetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Calabresi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Rita","family":"Bentivoglio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"13384_CR1","doi-asserted-by":"publisher","unstructured":"Ferguson LW, Rajput AH, Rajput A (2016) Early-onset vs. late-onset Parkinson\u2019s disease: a clinical-pathological study. 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