Raman Spectroscopy Analysis of Saliva and Salivary Extracellular Vesicles as New Biomarkers for Parkinson's Disease and Atypical Parkinsonisms.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor symptoms such as bradykinesia, tremor, rigidity and postural instability. An accurate rehabilitation program designed considering the specific characteristics of the patient allows you to maximize the effect of drug therapy, improve the patient's quality of life, while also limiting secondary complications related to the progression of the disease. At the time of diagnosis, however, it is particularly important to be able to quickly identify individuals with idiopathic Parkinson's and distinguish them from those who have an atypical form of Parkinsonism, such as Progressive Supranuclear Palsy (PSP), Multiple System Atrophy (MSA), Corticobasal Degeneration (CBD) and Dementia with Lewy bodies (DLB). Atypical Parkinsonisms are in fact progressive diseases that share some signs and symptoms with PD, however these patients do not respond as effectively to drug therapy since the cellular and degenerative mechanisms that characterize them are very different. For these reasons, their early identification is particularly important to identify the best pharmacological and rehabilitative path for each patient.

To ensure a more accurate patient profiling that takes into account the individual complex clinical picture, the discovery of a biomarker that can be periodically measured in an easily accessible biofluid would allow for better patient stratification, monitoring of the course of the disease and careful study of the effects of the pharmacological and rehabilitation program as well as its personalization, with a view to precision medicine designed, defined and built on the patient.

The Laboratory of Nanomedicine and Clinical Biophotonics (LABION) of Fondazione Don Gnocchi has been working for years on using innovative methods such as Raman spectroscopy to identify biomarkers of neurodegenerative diseases in easily accessible biological fluids, such as blood and saliva. Raman Spectroscopy (RS) allows to obtain a specific and complete characterization of a specific fluid in a rapid, sensitive and non-destructive way, without particular procedures for the preparation of the sample to be analyzed. In RS the entire spectrum obtained from the sample is used as a highly specific "fingerprint" for the selected sample (eg saliva, blood, serum, cerebrospinal fluid) which represents the diagnostic biomarker. The Raman analysis of saliva has already demonstrated the possibility of profiling patients with progressive pathologies with good accuracy and, specifically, of distinguishing subjects suffering from amyotrophic lateral sclerosis compared to subjects with other types of neurodegenerative diseases.

At the same time, LABION has verified the possibility of characterizing by Raman spectroscopy, the extracellular vesicles (EV) circulating in the blood of patients with PD. Since 2017, LABION has been working on the biochemical study of circulating EVs in the serum of PD patients by analyzing the EVs in spectroscopy and the ability of RS to identify a specific biochemical profile of blood vesicles that correlates with clinical scales has been demonstrated. UPDRS III and Hoehn and Yahr. The analysis of the EVs present in the saliva of patients with PD could help to understand the origin of biochemical alterations in the saliva as well as identify even more specific markers.

Raman spectroscopy is therefore proposed as a useful method for the rapid and comprehensive biochemical characterization of saliva and the vesicular component present within it, without the use of staining and labeling procedures.