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。

IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY
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
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引用次数: 0

摘要

目的:在我们之前的研究中,我们在新生PD患者中研究了针对不同分子途径的唾液生物标志物,包括α -突触核蛋白(a-syn)、tau病理、自噬(maplc3 β)和炎症(TNFalpha)。在这里,我们旨在研究这些唾液生物标志物的纵向变化,目的是评估它们随时间的动态变化及其对临床进展的预测价值。方法:对43名PD患者进行了为期4年的临床和分子随访(T1),这些患者来自我们先前分子表征的PD患者队列(T0)。采用ELISA法定量唾液中寡聚物和总a-syn、pS199-tau、总tau、活化map - lc3 β和TNFalpha的水平。临床评估包括运动和非运动症状量表。使用Wilcoxon检验来验证从T0到T1的分子和临床变化;回归分析T0时唾液生物标志物是否能预测临床进展,Spearman相关,探讨分子生物标志物变化与临床评分的相关性。结果:从T0到T1,寡聚a-syn和maplc3 β显著降低,而总a-syn、磷酸化tau、总tau和TNFalpha水平显著升高。低聚和总a-syn,磷酸化和总tau在基线预测运动进展,而TNFalpha预测非运动恶化。maplc3 β、磷酸化tau和TNFalpha与运动和非运动评分存在显著相关性,而在T0和T1时,a-syn物种与临床评分之间没有相关性。解释:唾液生物标志物动态反映PD进展并预测长期临床结果。这些发现支持将唾液作为预测和监测PD疾病进展的无创、可获取的来源。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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来源期刊
Annals of Clinical and Translational Neurology
Annals of Clinical and Translational Neurology Medicine-Neurology (clinical)
CiteScore
9.10
自引率
1.90%
发文量
218
审稿时长
8 weeks
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.
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