Understanding Alpha-Synuclein Spread in Parkinson's Disease Through Blood Biomarkers and Neuroimaging

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.

NCT Number	NCT07474779
Lead Sponsor	University of Pavia Collaborators: Pavia IRCCS Mondino di Pavia
Conditions	Parkinson's Disease (PD), GBA1 Parkinson Disease, REM Sleep Behavior Disorder (iRBD)
Enrollment	160 participants
Start Date	2026-05-11
Primary Completion	2028-12 (estimated)
Study Completion	2029-02 (estimated)
Updated on ClinicalTrials.gov	2026-05-01