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

NCT07480187 | Active Not Recruiting

• 1 other identifier: PNRR-MAD-2022-12376035
• Study Type: interventional
• Target: 340
• Locations: 1 country
• Sites: 3

Brief 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 patients affected by minor neurological symptoms (i.e., headache, peripheral neuropathy, etc.). The above-mentioned clinical information has been already collected for the retrospective cohort. Plasma amyloid-ß (Aß) 42/Aß40 ratio and phosphorylated at threonine 181 tau (p-tau) will be measured with the Lumipulse automated platform for all collected plasma samples. In a subset of 80 PD patients and 40 AD the CSF levels of this markers have been already measured and will be used to assess the robustness of these markers as well as the correlation between their CSF and plasma levels. SAA will be applied in OM for the detection of misfolded a-synuclein. Phosphorylated a-synuclein (p-a-syn) will be measured in a subset of PD patients and controls to compare the diagnostic accuracy of p-a-syn in skin biopsies and a-synuclein seeding activity in OM. In a subset of 30 PD and 30 AD/CTRL with paired OM and CSF samples the CSF SAA protocol of Amprion Inc. will be applied to verify the concordance of the results between CSF and OM. CNBP will be specifically responsible for collecting clinical and biomarker data from the three centers and for assessing their relationships. For the sake of measurements uniformity, the PEA analyses will be instead centralized at Olink (Uppsala, Sweden), at which the Olink Explore 384 Inflammation and Olink Explore 384 Neurology panels will be measured in all plasma samples.

Conditions

Parkinson Disease; Synucleinopathy; Alzheimer Disease

Keywords

biomarkers; CSF; plasma; skin; MRS; olfactory mucosa

Outcome Measures

Primary Outcomes (2)

• clinical or CSF-based diagnosis

  The clinical or cerebrospinal fluid (CSF)-based diagnosis will serve as the reference standard for the evaluation of biomarkers measured in blood, olfactory mucosa, and skin samples. Clinical diagnosis will be established according to the diagnostic criteria described by Daniel M. Postuma and colleagues in the Movement Disorders criteria for prodromal Parkinson's disease (2015). In participants undergoing lumbar puncture, CSF biomarkers including Aβ42/40 ratio, phosphorylated tau (p-tau181), and total tau (t-tau) will be measured to assess the presence of concomitant Alzheimer's disease pathology, using cut-off values established in previous international studies (e.g., Gobom et al., Clinical Chemistry and Laboratory Medicine, 2021). In addition, CSF α-synuclein seed amplification assays will be performed according to the protocol developed by Cheng Ma and colleagues and implemented in the Amprion platform (The Lancet Neurology, 2024).

  3 months

• Biological signature of Parkinson's disease

  Plasma proteomic profiling will be performed using proximity extension assay (PEA) technology to identify biomarker signatures associated with Parkinson's disease. In addition, plasma biomarkers related to neurodegeneration and Alzheimer's disease pathology, including phosphorylated tau (p-tau217), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP), will be measured in participants who do not undergo lumbar puncture. Clinical diagnosis and, when available, cerebrospinal fluid (CSF) biomarker results will be used as reference standards to identify blood-based biomarker profiles associated with Parkinson's disease. Additional peripheral biomarker assessments will include α-synuclein seed amplification assays performed on olfactory mucosa and skin biopsy samples. Proton magnetic resonance spectroscopy (¹H-MRS) of the brain will also be performed to explore metabolic signatures associated with Parkinson's disease.

  12 months

Study Arms (1)

biomarker analysis

EXPERIMENTAL

biomarker measurement in matched and unmatched biomatrices (blood, cerebrospinal fluid, skin biopses, brain metabolites by MRS, olfactory mucosa) collected by minimally-invasive procedures from patients with Parkinson's disease, Alzheimer's disease, and controls

Diagnostic Test: biomarkers

Interventions

biomarkers DIAGNOSTIC_TEST

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 spectroscopy.

biomarker analysis

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients with clinical diagnosis of Parkinson's disease, atypical parkinsonisms, Alzheimer's disease, healthy volunteers, people with subjective cognitive decline.

You may not qualify if:

• Other acute neurological diseases or neurodegenerative diseases such as Frontotemporal dementia, vascular dementia, and stroke
• Relevant comorbidities: chronic kidney disease (significant alteration of blood biomarkers)
• Skin biopsy: local skin infection at biopsy site, severe dermatologic disease at sampling area, known bleeding disorder, significant thrombocytopenia, anticoagulation not safely manageable, allergy to local anesthetics, poor wound healing, severe peripheral vascular disease, high-risk immunosuppression, inability to consent or cooperate, extensive scarring at intended site
• Magnetic resonance spectroscopy: non-MRI-compatible implanted device, ferromagnetic intracranial clip, metallic foreign body, severe claustrophobia not manageable, inability to remain still, MRI-conditional device not meeting safety conditions, pregnancy per institutional policy, severe agitation or confusion, body size exceeding scanner limits, severe motion disorder affecting acquisition
• Venipuncture: refusal or inability to consent, local infection at puncture site, severe coagulopathy, marked thrombocytopenia, high bleeding risk anticoagulation, severe anemia relative to planned blood volume, difficult venous access, history of severe vasovagal syncope
• Eligibility Criteria
• Adults able to provide informed consent
• Clinical diagnosis of Parkinson's disease
• Clinical diagnosis of atypical parkinsonism
• Clinical diagnosis of Alzheimer's disease
• Individuals with subjective cognitive decline
• Healthy volunteers
• Acute neurological diseases
• Other neurodegenerative diseases not included in the study groups (e.g., frontotemporal dementia, vascular dementia)
• History of stroke with significant neurological sequelae

Sponsors & Collaborators

• Azienda Ospedaliera di Perugia: lead
• Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta: collaborator
• IRCCS Centro Neurolesi Bonino Pulejo: collaborator

Study Sites (3)

Centro Neurolesi Bonino Pulejo

Messina, Messina, 98124, Italy

Location

Istituto Neurologico Carlo Besta

Milan, Milano, 20133, Italy

Location

Azienda Ospedaliera di Perugia

Perugia, 06129, Italy

Location

MeSH Terms

Conditions

Parkinson Disease; Synucleinopathies; Alzheimer Disease

Interventions

Environmental Biomarkers

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Dementia; Tauopathies; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Biomarkers; Biological Factors; Biological Phenomena; Environmental Monitoring; Environmental Exposure; Environmental Pollution; Public Health; Environment and Public Health

Study Officials

• Lucilla Parnetti, MD, PhD

  Azienda Ospedaliera di Perugia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of the Neurology Clinic

Model Details: 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

Study Record Dates

• First Submitted: March 2, 2026
• First Posted: March 18, 2026
• Study Start: May 20, 2023
• Primary Completion: February 17, 2025
• Study Completion: May 20, 2026
• Last Updated: March 18, 2026

Record last verified: 2026-03

Locations

IT (3)