Maria Ilenia De Bartolo, Daniele Belvisi, Matteo Costanzo, Claudia Caturano, Francesco Emanuele Bellomi, Carolina Cutrona, Flavia Aiello, Giorgio Leodori, Massimo Marano, Romina Mancinelli, Antonella Conte, Giovanni Fabbrini, Alfredo Berardelli, Giorgio Vivacqua
{"title":"唾液生物标志物在帕金森病临床分子进展定义中的纵向研究。","authors":"Maria Ilenia De Bartolo, Daniele Belvisi, Matteo Costanzo, Claudia Caturano, Francesco Emanuele Bellomi, Carolina Cutrona, Flavia Aiello, Giorgio Leodori, Massimo Marano, Romina Mancinelli, Antonella Conte, Giovanni Fabbrini, Alfredo Berardelli, Giorgio Vivacqua","doi":"10.1002/acn3.70178","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>In our previous study, we investigated in de novo PD patients salivary biomarkers targeting different molecular pathways, including alpha-synuclein (a-syn), 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.</p><p><strong>Methods: </strong>A clinical and molecular 4-year follow-up (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-syn, pS199-tau, total-tau, activated MAP-LC3beta, and TNFalpha were quantified using ELISA. Clinical assessments included motor and non-motor 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.</p><p><strong>Results: </strong>Oligomeric a-syn and MAPLC3beta dramatically decrease, while total a-syn, phosphorylated-tau, total-tau, and TNFalpha exhibited significantly higher levels from T0 to T1. Oligomeric and total a-syn, phosphorylated and total-tau at baseline predicted motor progression, while TNFalpha predicted non-motor worsening. Significant correlations were found for MAPLC3beta, phosphorylated tau, and TNFalpha with motor and non-motor scores, while no correlations emerged between a-syn species and clinical scores both at T0 and T1.</p><p><strong>Interpretation: </strong>Salivary biomarkers dynamically reflect PD progression and predict long-term clinical outcomes. These findings support the use of saliva as a noninvasive, accessible source for predicting and monitoring disease progression in PD.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Longitudinal Study of Salivary Biomarkers in the Definition of Clinico-Molecular Progression of Parkinson's Disease.\",\"authors\":\"Maria Ilenia De Bartolo, Daniele Belvisi, Matteo Costanzo, Claudia Caturano, Francesco Emanuele Bellomi, Carolina Cutrona, Flavia Aiello, Giorgio Leodori, Massimo Marano, Romina Mancinelli, Antonella Conte, Giovanni Fabbrini, Alfredo Berardelli, Giorgio Vivacqua\",\"doi\":\"10.1002/acn3.70178\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>In our previous study, we investigated in de novo PD patients salivary biomarkers targeting different molecular pathways, including alpha-synuclein (a-syn), 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.</p><p><strong>Methods: </strong>A clinical and molecular 4-year follow-up (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-syn, pS199-tau, total-tau, activated MAP-LC3beta, and TNFalpha were quantified using ELISA. Clinical assessments included motor and non-motor 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.</p><p><strong>Results: </strong>Oligomeric a-syn and MAPLC3beta dramatically decrease, while total a-syn, phosphorylated-tau, total-tau, and TNFalpha exhibited significantly higher levels from T0 to T1. Oligomeric and total a-syn, phosphorylated and total-tau at baseline predicted motor progression, while TNFalpha predicted non-motor worsening. Significant correlations were found for MAPLC3beta, phosphorylated tau, and TNFalpha with motor and non-motor scores, while no correlations emerged between a-syn species and clinical scores both at T0 and T1.</p><p><strong>Interpretation: </strong>Salivary biomarkers dynamically reflect PD progression and predict long-term clinical outcomes. These findings support the use of saliva as a noninvasive, accessible source for predicting and monitoring disease progression in PD.</p>\",\"PeriodicalId\":126,\"journal\":{\"name\":\"Annals of Clinical and Translational Neurology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2025-09-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of Clinical and Translational Neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/acn3.70178\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Clinical and Translational Neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/acn3.70178","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Longitudinal Study of Salivary Biomarkers in the Definition of Clinico-Molecular Progression of Parkinson's Disease.
Objectives: In our previous study, we investigated in de novo PD patients salivary biomarkers targeting different molecular pathways, including alpha-synuclein (a-syn), 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.
Methods: A clinical and molecular 4-year follow-up (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-syn, pS199-tau, total-tau, activated MAP-LC3beta, and TNFalpha were quantified using ELISA. Clinical assessments included motor and non-motor 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.
Results: Oligomeric a-syn and MAPLC3beta dramatically decrease, while total a-syn, phosphorylated-tau, total-tau, and TNFalpha exhibited significantly higher levels from T0 to T1. Oligomeric and total a-syn, phosphorylated and total-tau at baseline predicted motor progression, while TNFalpha predicted non-motor worsening. Significant correlations were found for MAPLC3beta, phosphorylated tau, and TNFalpha with motor and non-motor scores, while no correlations emerged between a-syn species and clinical scores both at T0 and T1.
Interpretation: Salivary biomarkers dynamically reflect PD progression and predict long-term clinical outcomes. These findings support the use of saliva as a noninvasive, accessible source for predicting and monitoring disease progression in PD.
期刊介绍:
Annals of Clinical and Translational Neurology is a peer-reviewed journal for rapid dissemination of high-quality research related to all areas of neurology. The journal publishes original research and scholarly reviews focused on the mechanisms and treatments of diseases of the nervous system; high-impact topics in neurologic education; and other topics of interest to the clinical neuroscience community.