Toward Molecular Profiling of Parkinson's Disease in Easily Accessible Biological Matrices

Official Summary

Parkinson's disease (PD) is a synucleinopathy and the most common neurodegenerative disease involving disabling motor deficits. PD is clinically heterogeneous; motor symptoms may be accompanied by nonmotor symptoms such as cognitive impairment. Many molecular processes may underlie the phenotypic heterogeneity of PD, among which synaptic and axonal degeneration, neuroinflammation, and the co-occurrence of different proteinopathies. The definition of robust biomarkers that reflect distinct pathophysiological pathways taking place in PD may favor the selection of more homogeneous cohorts of patients in clinical trials, thus increasing the chance of success of a targeted disease-modifying therapy. The possibility of measuring these markers in biological matrices suitable for repeated sampling could provide objective measures of the effectiveness of a therapeutic approach. In this proposal we will combine the expertise of three different Italian medical research centers to establish a molecular profile of PD based on biomarkers reflecting different biological pathways, in different biological matrices, by applying immunoassays, proximity extension assays (PEA) and seed amplification assays (SAA). Two easily accessible biological matrices, i.e., blood plasma and olfactory mucosa (OM), has been/will be collected in each center for PD patients, controls and patients affected by Alzheimer's disease (AD) as other neurodegenerative disease controls. OM will be collected by a non-invasive procedure known as nasal brushing which is already operational and standardized among the three participating centers. The project will include both a prospective and retrospective cohort composed of 200 PD patients, 100 controls and 40 AD. All PD patients that will be recruited will undergo a thorough clinical and neuropsychological evaluation. The control group will be constituted by healthy volunteers as well as by cognitively unimpaired subjects with subjective memory complaints or patien

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 340 participants

Interventions

• DIAGNOSTIC_TEST: biomarkers — Comparison of biomarkers measured in matched and unmatched biomatrices (blood, cerebrospinal fluid, skin biopses, brain metabolites by MRS, olfactory mucosa) in patients with Parkinson's disease, Alzheimer's disease, and controls. These biomarkers include cerebrospinal fluid biomarkers of Alzheimer's disease, proximity-extension assay proteomic biomarkers, alpha-synuclein seed amplification assay performed in olfactory mucosa, cerebrospinal fluid and skin, and brain magnetic resonance spectrosco

Primary Outcomes

• clinical or CSF-based diagnosis (3 months)
• Biological signature of Parkinson's disease (12 months)

Trial Locations

• Centro Neurolesi Bonino Pulejo, Messina, Messina, Italy
• Istituto Neurologico Carlo Besta, Milan, Milano, Italy
• Azienda Ospedaliera di Perugia, Perugia, Italy

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