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We therefore investigated whether the biological profile at PD onset, as defined through a panel of CSF biomarkers, may predispose to the development of MC.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We conducted a dual-center retrospective longitudinal study involving 131 de novo (DN) PD patients (newly diagnosed, untreated). At baseline, patients were evaluated by motor and non-motor scores, and the measurement of CSF total \u03b1-synuclein (\u03b1-syn), total and phosphorylated-181-tau (t-tau, p-tau), amyloid-\u03b242 and amyloid-\u03b240 (A\u03b242, A\u03b240) levels, p-tau\/t-tau, A\u03b242\/A\u03b240, and p-tau\/A\u03b242 ratios. According to the successive development of MC, patients were classified as \u201cwith MC\u201d (wMC) or \u201cwithout MC\u201d (noMC). A control group of 107 controls was also collected. Variables were compared between groups, adjusting for main covariates; ROC and Cox analyses evaluated predictive values.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The DN PD cohort was followed for 57 (\u00b1\u200918) months, with 38 (29%) patients developing MC. At baseline, DN patients showed lower CSF total \u03b1-syn and t-tau levels than controls. The wMC group had higher p-tau, p-tau\/t-tau, and p-tau\/A\u03b242 ratios than noMC. The p-tau\/t-tau ratio best predicted MC development; above the cutoff of 0.148, MC were 2.6 times more likely with 81% sensitivity and 61% specificity (AUC\u2009=\u20090.79).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Elevated CSF p-tau\/t-tau ratio in DN PD patients predicts higher MC risk, supporting biomarker-based stratification for patients at onset. Our findings also highlight Alzheimer\u2019s co-pathology, especially tauopathy, as a key factor in shaping PD motor progression from early stages.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00415-025-13325-4","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T09:49:54Z","timestamp":1755078594000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["CSF phospho-tau levels at Parkinson\u2019s disease onset predict the risk for development of motor complications"],"prefix":"10.1007","volume":"272","author":[{"given":"Jacopo","family":"Bissacco","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Di Lazzaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Bovenzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia Maria","family":"Sancesario","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Conti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Simonetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Mascioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Mancini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Buttarazzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariangela","family":"Pierantozzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Pieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Bernardini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Stefani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Rita","family":"Bentivoglio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Calabresi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola Biagio","family":"Mercuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2517-6278","authenticated-orcid":false,"given":"Tommaso","family":"Schirinzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"13325_CR1","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/S0140-6736(23)01478-2","volume":"403","author":"HR Morris","year":"2024","unstructured":"Morris HR, Spillantini MG, Sue CM, Williams-Gray CH (2024) The pathogenesis of Parkinson\u2019s disease. 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GDL: the author declares that there are no additional disclosures to report. RB: the author declares that there are no additional disclosures to report. GMS: the author declares that there are no additional disclosures to report. MC: the author declares that there are no additional disclosures to report. CS: the author declares that there are no additional disclosures to report. DM: the author declares that there are no additional disclosures to report. MM: the author declares that there are no additional disclosures to report. VB: the author declares that there are no additional disclosures to report. MarPier: MNESYS (PE0000006) grant by Italian Ministry of University and Research. MasPier: the author declares that there are no additional disclosures to report. SB: the author declares that there are no additional disclosures to report. AS: MNESYS (PE0000006) grant by Italian Ministry of University and Research; PNRR-MAD-2022\u201312376769 Grant by Italian Ministry of Health. ARB: the author declares that there are no additional disclosures to report. PC: the author declares that there are no additional disclosures to report. NBM: MNESYS (PE0000006) grant by Italian Ministry of University and Research; PRIN 2022 Grant by Italian Ministry of University and Research; PNRR-MAD-2022\u201312376556 Grant by Italian Ministry of Health. TS: PRIN 2022\u2014Grant from the Italian Ministry of University and Research; PNRR PE00000019\u2014HEAL ITALIA\u2014PE6\u2014Grant from the Italian Ministry of University and Research.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Written informed consent was obtained from every participant. The study was approved by the local ethical committee (protocol n\u00b0 64\/20) and conducted in agreement with the principles of the Helsinki declarations. We confirm that we have read the Journal\u2019s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"573"}}