{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:49:18Z","timestamp":1790192958943,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T00:00:00Z","timestamp":1758931200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>In our previous study, we investigated in de novo PD patients salivary biomarkers targeting different molecular pathways, including alpha\u2010synuclein (a\u2010syn), tau pathology, autophagy (MAPLC3beta), and inflammation (TNFalpha). Here, we aimed to investigate longitudinal changes in these salivary biomarkers with the goal of assessing their dynamic changes over time and their predictive value for clinical progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A clinical and molecular 4\u2010year follow\u2010up (T1) was conducted on 43 PD patients of our previously molecularly characterized cohort of de novo PD patients (T0). Salivary levels of oligomeric and total a\u2010syn, pS199\u2010tau, total\u2010tau, activated MAP\u2010LC3beta, and TNFalpha were quantified using ELISA. Clinical assessments included motor and non\u2010motor symptom scales. The Wilcoxon test was used to verify molecular and clinical variations from T0 to T1; regression analysis to determine whether salivary biomarkers at T0 could predict clinical progression and Spearman's correlations to explore correlations between changes in molecular biomarkers and clinical scores.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Oligomeric a\u2010syn and MAPLC3beta dramatically decrease, while total a\u2010syn, phosphorylated\u2010tau, total\u2010tau, and TNFalpha exhibited significantly higher levels from T0 to T1. Oligomeric and total a\u2010syn, phosphorylated and total\u2010tau at baseline predicted motor progression, while TNFalpha predicted non\u2010motor worsening. Significant correlations were found for MAPLC3beta, phosphorylated tau, and TNFalpha with motor and non\u2010motor scores, while no correlations emerged between a\u2010syn species and clinical scores both at T0 and T1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Salivary biomarkers dynamically reflect PD progression and predict long\u2010term clinical outcomes. These findings support the use of saliva as a noninvasive, accessible source for predicting and monitoring disease progression in PD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70178","type":"journal-article","created":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T11:14:41Z","timestamp":1758971681000},"page":"122-130","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Longitudinal Study of Salivary Biomarkers in the Definition of Clinico\u2010Molecular Progression of Parkinson's Disease"],"prefix":"10.1002","volume":"13","author":[{"given":"Maria Ilenia","family":"De Bartolo","sequence":"first","affiliation":[{"name":"Department of Radiological Sciences, Oncology and Anatomical Pathology Sapienza University of Rome  Rome Italy"},{"name":"IRCCS Neuromed  Pozzilli 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Emanuele","family":"Bellomi","sequence":"additional","affiliation":[{"name":"Department of Experimental Morphology and Microscopy, Integrated Research Center (PRAAB) Campus Biomedico University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Cutrona","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences Sapienza University of Rome  Rome Italy"},{"name":"Department of Neurology and Stroke Unit San Giovanni Addolorata Hospital  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Aiello","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Leodori","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed  Pozzilli Italy"},{"name":"Department of Human Neurosciences Sapienza University of Rome  Rome 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