Understanding Alpha-Synuclein Spread in Parkinson's Disease Through Blood Biomarkers and Neuroimaging
Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Pavia
About this trial
The project aims to investigate how abnormal accumulation of alpha synuclein and its interaction with tau influence brain function across the Parkinson's disease (PD) spectrum, with particular focus on individuals carrying GBA1 mutations. This interventional, monocentric, cross sectional study includes patients with PD, individuals with idiopathic REM sleep behavior disorder, and participants without PD.
All enrolled subjects will undergo clinical and neuropsychological assessments, blood based biomarker analyses related to neurodegeneration, synaptic and mitochondrial function, and multimodal brain MRI to evaluate brain structure, white matter integrity, and functional connectivity.
The study aims to:
* characterize the relationship between alpha synuclein/tau pathology and synaptic mitochondrial dysfunction; * identify biomarker and connectivity signatures across disease stages and genetic backgrounds; * integrate preclinical, clinical, biological, and imaging data to support the development of mechanistic models of alpha synuclein propagation.
In parallel, preclinical studies in GBA PD mouse models and wild type mice will be used to investigate how changes in PD-related pathology (alpha-synuclein and tau) relates to behavior, brain imaging alterations and mitochondrial, axonal and synaptic damage. Animal model will also aid the validation of a new PET tracer that targets alpha synuclein (i.e., \[¹⁸F\]Syntacasyn).
Together, human and preclinical studies are designed to provide a translational framework integrating molecular changes with brain network alterations and clinical heterogeneity in PD.
Eligibility criteria
Qualifiers
Diagnosis of PD according to MDS-PD criteria and, for the GBA-PD group, presence of heterozygous GBA mutations (with a balanced distribution of severe, risk, mild, and complex variants);
Disease duration between 3 and 7 years;
Disease stage according to Hoehn & Yahr ≤ 3;
Absence of mutations in other known genes associated with PD susceptibility;
Disqualifiers
Diagnosis of atypical and/or secondary parkinsonism;
Diagnosis of dementia according to DSM-5 criteria;
Presence of other neurological disorders and/or essential tremor;
Presence of systemic inflammatory or infectious diseases, autoimmune diseases, or malignant tumors at the time of enrollment.
Trial design
Treatments tested in this trial
- brain imaging
- blood draw
- Skin biopsy
Treatment groups
160 Participants
are divided into 6 treatment groups6
Treatment groupsSee each treatment group below.
Sponsors and collaborators
University of Pavia
Lead sponsor
Pavia IRCCS Mondino di Pavia
Collaborator
Source ClinicalTrials.gov