# Longitudinal Study of Salivary Biomarkers in the Definition of Clinico‐Molecular Progression of Parkinson's Disease

## TL;DR

This study tracks salivary biomarkers in Parkinson's patients over four years to see how they change and predict disease progression.

## Contribution

The study identifies longitudinal changes in salivary biomarkers and their predictive value for clinical progression in Parkinson's disease.

## Key findings

- Oligomeric a-syn and MAPLC3beta decreased, while total a-syn, phosphorylated-tau, total-tau, and TNFalpha increased over four years.
- Baseline levels of certain biomarkers predicted motor and non-motor symptom progression.
- Salivary biomarkers correlate with clinical scores, supporting their use in monitoring Parkinson's progression.

## Abstract

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.

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.

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.

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.

Longitudinal changes in salivary biomarkers in Parkinson’s disease (PD) from early (T0) to 4‐year follow‐up (T1), quantified by ELISA: oligomeric and total α‐synuclein, total and phosphorylated tau, MAP1LC3B (autophagy), and TNFa (inflammation). Blue arrows indicate direction of change at T1 vs T0 (up = increase; down = decrease). The right‐hand panel displays each baseline (T0) marker’s relative contribution to predicting motor and non‐motor symptom progression.