Objective: Investigate longitudinal changes in salivary levels of oligomeric and total a-synuclein (a-syn), phosphorylated-tau (p-tau), total tau, MAP-LC3, and TNFa in Parkinson’s Disease (PD) patients

Assess whether salivary biomarkers at disease onset can predict clinical worsening over time.

Correlate longitudinal changes in molecular and clinical data

Verify longitudinal change in biomarkers accuracy in discriminating PD patients from Healthy Controls (HC)

Background: Among neurodegenerative disorders, PD exhibits the fastest-growing incidence worldwide[1], highlighting the urgent need for non-invasive biomarkers. Saliva presents a promising non-invasive sample for the search of biomarkers in PD[2]. In our previous study, we investigated salivary biomarkers targeting different molecular pathways, including alpha-synuclein (a-syn) and tau pathology, autophagy (MAP-LC3b), and inflammation (TNFa), in de novo PD patients. This analysis demonstrated high accuracy for oligomeric a-syn(AUC=0.99) and MAPLC3(AUC=0.92) in discriminating PD patients from HC[3]

Method: A clinical and molecular 4-year follow-up (T1) was conducted on 40 PD patients of the previous cohort[3]. Levels of oligomeric and total a-syn, p-tau, total tau, MAP-LC3, and TNFa were quantified using ELISA. Clinical assessments at T1 included motor and non-motor symptoms scales[3]. Statistical analyses included the Wilcoxon test to evaluate molecular and clinical changes from T0 to T1; regression analysis to determine whether salivary biomarkers at T0 could predict clinical progression; Spearman’s correlations to explore correlations between changes in molecular biomarkers and clinical scores; ROC analysis to verify biomarkers accuracy at T1 in discriminating PD patients from HC

Results: Oligomeric a-syn and MAPLC3b showed significantly lower salivary levels, while total a-syn, p-tau, total-tau and TNFa exhibited significantly higher salivary levels from T0 to T1 Fig1. Oligomeric and total a-syn, total-tau and TNFa at T0 were able to predict the worsening of motor symptoms, while MAPLC3 to predict the worsening of non motor symptoms. Changes in TNFa positively correlated with worsening of cognition functions. Accuracy was for oligo a-syn:80%, total a-syn:98%, TNFa:100%, MAPLC3:63%, p-tau:100%, total tau:99% Fig2

Conclusion: These findings support the potential of salivary biomarkers for both diagnostic and predictive applications in PD, warranting further validation in larger cohorts.

Fig1

Fig2

References: [1] GBD 2016 Parkinson’s Disease Collaborators. Global, regional, and national burden of Parkinson’s disease, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018 Nov;17(11):939-953.
[2] De Bartolo MI, Belvisi D, Mancinelli R, Costanzo M, Caturano C, Leodori G, Berardelli A, Fabbrini G, Vivacqua G. A systematic review of salivary biomarkers in Parkinson’s disease. Neural Regen Res. 2024 Dec.
[3] De Bartolo MI, Vivacqua G, Belvisi D, Mancinelli R, Fabbrini A, Manzo N, Costanzo M, Leodori G, Conte A, Fabbrini G, Morini S, Berardelli A. A Combined Panel of Salivary Biomarkers in de novo Parkinson’s Disease. Ann Neurol. 2023 Mar;93(3):446-459.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/salivary-biomarkers-in-parkinsons-disease-a-follow-up-study/