Early diagnosis of Neurodegenerative diseases (NDDs) and accurate patient profiling are key goals needed to tailor prompt personalized therapeutic strategies that can significantly impact disease progression and patients' quality of life. The project will validate a novel, cost-effective and quick biophotonic-based method for early and differential diagnosis of NDDs (Parkinson's disease, atypical parkinsonisms, Alzheimer's disease) and for routine clinical monitoring of NDD progression (longitudinal study). Raman spectroscopy (RS) will be applied to biochemically profile saliva and salivaderived Extracellular Vesicles (sEVs) and to identify a spectroscopic biomarker for NDDs. Optimized protocols for RS will be used to concomitantly evaluate saliva and sEVs from people with NDDs and to detect salivary changes in the biochemical profile, with special focus on EV-associated components. The accuracy of the method in discriminating NDDs at different disease stages and during disease progression will be verified. A nanotechnology-based biomolecular characterization of saliva and sEV will clarify the involvement of specific pathological molecules in NDDs progression.
AD: standard criteria for dementia due to AD with AD neurochemical demonstration.
PD: MDS Criteria; modified Hoehn&Yahr stages; stable pharmacological treatment (last 4 weeks).
AtP: current consensus diagnostic criteria for progressive supranuclear palsy; corticobasal degeneration and multiple system atrophy.
prodromic PD: according to diagnostic criteria by Berg;
For all the experimental groups considered, subjects with concomitant chronic and / or inflammatory diseases of the oral cavity, other systemic diseases, oncological or infectious diseases will be excluded.
Patients not able to provide written informed consent autonomously will be excluded.
For PD patients: Vascular, familiar and drug- induced parkinsonism, other known or suspected causes (metabolic, brain tumor etc) or any suggestive features of AtP; dementia with MoCA Test Correct Score<15
Recruitment will take place at Diagnostic and Rehabilitation Center for Parkinson's Disease and Parkinsonism (DiaRiaPARK) of the U.O. of Rehabilitative Neurology of IRCCS S. Maria Nascente (MILAN) of Fondazione Don Carlo Gnocchi and at PROMISE@LAB of IRCCS Don Gnocchi (FLORENCE) of Fondazione Don Gnocchi (FDG). After emedation of the trial protocol and approval by the Local Ethical Committees, recruitment will take place also at Centro S. Maria ai Servi (PARMA), AOU Careggi (FLORENCE) and IRCCS Istituto Neurologico Carlo Besta (MILAN).
Cohort
Prospective
Saliva collection, longitudinal
Other intervention1 ml of saliva will be collected with Salivette swabs. Subjects will undergo assessments and saliva sampling at enrollment time (T0) and one year after (T12).
Salivary Raman fingerprint of AD, PD, AtPD, prodromal PD and MCI
Differences in the Raman spectra of saliva of patients with AD, PD, AtPD, prodromal PD and MCI in the spectral range 400-1800 cm-1
Raman fingerprint of salivary EV of AD, PD, AtPD, prodromal PD and MCI
Differences in the Raman spectra of saliva derived EVs of patients with AD, PD, AtPD, prodromal PD and MCI in the spectral ranges 600-1800 cm-1 and 2600-3200 cm-1
Salivary NDD biomarkers
Quantification of NDDs related markers by SiMoA technology: * asyn for PD, AtP and pPD * Aβ1-42 for AD and MCI * NfL as general biomarkers of neurological damage in all groups. Changes in concentration are expected between groups and for the same patient between T0 and T12.
Salivary Raman fingerprint of patients after 1 year
Changes in the Raman spectra of saliva between T0 (enrollment) and T12 (1 year after enrollment) associated to disease progression.
Salivary EV Raman fingerprint of patients after 1 year
Changes in the Raman spectra of saliva derived EVs between T0 (enrollment) and T12 (1 year after enrollment) associated to disease progression.
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Fondazione Don Carlo Gnocchi Onlus
Lead sponsor
Fondazione Regionale per la Ricerca Biomedica
Collaborator
Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
Collaborator
Azienda Ospedaliero-Universitaria Careggi
Collaborator
