Understanding Alpha-Synuclein Spread in Parkinson's Disease Through Blood Biomarkers and Neuroimaging
SYNchronPD
From Genes to Virtual Brain: Defining the Pathogenic Mechanisms Promoting Alfa-synuclein Seeding and Spreading in Parkinson's Disease.
1 other identifier
interventional
160
1 country
2
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started May 2026
Typical duration for not_applicable
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 6, 2026
CompletedFirst Posted
Study publicly available on registry
March 16, 2026
CompletedStudy Start
First participant enrolled
May 11, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2028
Study Completion
Last participant's last visit for all outcomes
February 1, 2029
May 1, 2026
March 1, 2026
2.6 years
March 6, 2026
April 27, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Concentration of alpha-synuclein levels in plasma
Quantification of levels of Total alpha-synuclein and 129P-alpha-synuclein (pg/ml) in neuronal-derived extracellular vesicles using ultrasensitive immunoassays (NULISA).
Baseline visit
Concentration of tau levels in plasma
Quantification of total-tau and p-tau18 (pg/ml) in neuronal-derived extracellular vesicles using ultrasensitive immunoassays (NULISA).
Baseline visit
Investigation of glucocerebrosidase activity in Peripheral Blood Mononuclear Cells
Glucocereborsidase activity will be estimated in Peripheral Blood Mononuclear Cells usign a flourimetry assay
Baseline visit
Secondary Outcomes (6)
Assessment of mitochondrial damage in plasma
Baseline visit
Plasma synaptic protein concentration
Baseline visit
Brain network connectivity in Parkinson's disease
Baseline visit
In vitro neuronal responses in hiPSC-derived dopaminergic neurons
Baseline visit
Estimation of synaptic damage in Neuronal extracellular vesicle
Baseline visit
- +1 more secondary outcomes
Other Outcomes (1)
Comprehensive clinical and neuropsychological assessement
Baseline visit
Study Arms (6)
GBA-PD
EXPERIMENTALDiagnostic Test: brain imaging Procedure/Surgery: blood draw, skin biopsy
nonGBA-PD
EXPERIMENTALDiagnostic Test: brain imaging Procedure/Surgery: blood draw, skin biopsy
nonGBA-iRBD
EXPERIMENTALDiagnostic Test: brain imaging Procedure/Surgery: blood draw, skin biopsy
GBA-iRBD
EXPERIMENTALDiagnostic Test: brain imaging Procedure/Surgery: blood draw, skin biopsy
GBA-nonPD
EXPERIMENTALDiagnostic Test: brain imaging Procedure/Surgery: blood draw
Healthy controls
EXPERIMENTALDiagnostic Test: brain imaging Procedure/Surgery: blood draw
Interventions
Participants will undergo a single brain MRI acquisition, including structural, diffusion-weighted, and resting-state functional MRI.
Collection of a venous blood sample for biochemical analyses
A small punch skin biopsy (about 3-4 mm) will be performed under local anesthesia on a small sample of enrolled participants (n=10)
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- 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.
- Presence of systemic inflammatory or infectious diseases, autoimmune diseases, or malignant tumors at the time of enrollment;
- Diagnosis of atypical and/or secondary parkinsonism;
- Diagnosis of dementia according to DSM-5 criteria.
- 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;
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Pavialead
- Pavia IRCCS Mondino di Paviacollaborator
Study Sites (2)
Neurological Institute Foundation Casimiro Mondino
Pavia, PV, 27100, Italy
University of Pavia
Pavia, PV, 27100, Italy
Related Publications (6)
Baden P, Perez MJ, Raji H, Bertoli F, Kalb S, Illescas M, Spanos F, Giuliano C, Calogero AM, Oldrati M, Hebestreit H, Cappelletti G, Brockmann K, Gasser T, Schapira AHV, Ugalde C, Deleidi M. Glucocerebrosidase is imported into mitochondria and preserves complex I integrity and energy metabolism. Nat Commun. 2023 Apr 6;14(1):1930. doi: 10.1038/s41467-023-37454-4.
PMID: 37024507BACKGROUNDNeumann J, Bras J, Deas E, O'Sullivan SS, Parkkinen L, Lachmann RH, Li A, Holton J, Guerreiro R, Paudel R, Segarane B, Singleton A, Lees A, Hardy J, Houlden H, Revesz T, Wood NW. Glucocerebrosidase mutations in clinical and pathologically proven Parkinson's disease. Brain. 2009 Jul;132(Pt 7):1783-94. doi: 10.1093/brain/awp044. Epub 2009 Mar 13.
PMID: 19286695BACKGROUNDVogel JW, Corriveau-Lecavalier N, Franzmeier N, Pereira JB, Brown JA, Maass A, Botha H, Seeley WW, Bassett DS, Jones DT, Ewers M. Connectome-based modelling of neurodegenerative diseases: towards precision medicine and mechanistic insight. Nat Rev Neurosci. 2023 Oct;24(10):620-639. doi: 10.1038/s41583-023-00731-8. Epub 2023 Aug 24.
PMID: 37620599BACKGROUNDPan L, Li C, Meng L, Tian Y, He M, Yuan X, Zhang G, Zhang Z, Xiong J, Chen G, Zhang Z. Tau accelerates alpha-synuclein aggregation and spreading in Parkinson's disease. Brain. 2022 Oct 21;145(10):3454-3471. doi: 10.1093/brain/awac171.
PMID: 35552614BACKGROUNDGuo M, Wang J, Zhao Y, Feng Y, Han S, Dong Q, Cui M, Tieu K. Microglial exosomes facilitate alpha-synuclein transmission in Parkinson's disease. Brain. 2020 May 1;143(5):1476-1497. doi: 10.1093/brain/awaa090.
PMID: 32355963BACKGROUNDRecasens A, Dehay B. Alpha-synuclein spreading in Parkinson's disease. Front Neuroanat. 2014 Dec 18;8:159. doi: 10.3389/fnana.2014.00159. eCollection 2014.
PMID: 25565982BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- PhD
Study Record Dates
First Submitted
March 6, 2026
First Posted
March 16, 2026
Study Start (Estimated)
May 11, 2026
Primary Completion (Estimated)
December 1, 2028
Study Completion (Estimated)
February 1, 2029
Last Updated
May 1, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share