Blood tests and brain imaging to study alpha-synuclein in Parkinson's disease
Studies alpha-synuclein spread using blood tests and brain scans in Parkinson's disease.
Plain-language title generated from the registry record
Registry title: Understanding Alpha-Synuclein Spread in Parkinson's Disease Through Blood Biomarkers and Neuroimaging
Key facts
- Where
- Pavia, ItalySee the 2 sites
Where in Italy
- Neurological Institute Foundation Casimiro MondinoPavia, ItalyNo longer taking part
- University of PaviaPavia, ItalyNo longer taking part
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Trial details
- Who runs it
- University of Pavia
- Trial code
- NCT07474779
- Record updated
- 1 May 2026
- Original description
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.Read full original descriptionShow less
From Genes to Virtual Brain: Defining the Pathogenic Mechanisms Promoting Alfa-synuclein Seeding and Spreading in Parkinson's Disease.
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.
Inclusion: 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; Age > 18 Years; Ability to understand and voluntarily sign informed consent and to comply with study procedures; Age > 18 Years; Ability to understand and voluntarily sign informed consent and to comply with study procedures; No diagnosis of PD or other neurological disorders; Presence of a heterozygous GBA mutation for the GBA-nonPD group and absence of such mutation for control subjects (nonGBA-nonPD); Absence of mutations in other known genes associated with PD susceptibility; Diagnosis of idiopathic REM Sleep Behavior Disorder according to ICSD-3; Age > 18 Years; Ability to understand and voluntarily sign informed consent and to comply with study procedures; No diagnosis of PD or other neurological disorders; Presence of a heterozygous GBA mutation for the GBA-iRBD group and absence of such mutation for the nonGBA-iRBD group; Absence of mutations in other known genes associated with PD susceptibility.
Exclusion: 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; Presence of systemic inflammatory or infectious diseases, autoimmune diseases, or malignant tumors at the time of enrollment; Diagnosis of dementia according to DSM-5 criteria; Presence of systemic inflammatory or infectious diseases, autoimmune diseases, or malignant tumors at the time of enrollment; Diagnosis of dementia according to DSM-5 criteria; Diagnosis of atypical and/or secondary parkinsonism; Diagnosis of atypical and/or secondary parkinsonism; Diagnosis of atypical and/or secondary parkinsonism.