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Radiological markers of CSF α-synuclein aggregation in Parkinson's disease patients
Amgad Droby1,2,3,4, Avital Yoffe-Vasiliev5,6, Daniel Atias5,6
1Movement Disorders Unit, Neurological Institute, Tel Aviv Medical Center, Tel Aviv, Israel. amgadd@tlvmc.gov.il.
NPJ Parkinson'S Disease
|January 3, 2025
Summary
Alpha-synuclein aggregation, a Parkinson's disease hallmark, correlates with reduced brain volumes and altered connectivity. Synuclein amplification assays reveal these changes, potentially indicating disease severity in Parkinson's patients.
Area of Science:
- Neuroscience
- Neurology
- Radiology
Background:
- Alpha-synuclein (αS) aggregation is a key pathological hallmark of Parkinson's disease (PD).
- Synuclein amplification assays (SAA) detect αS aggregation in cerebrospinal fluid (CSF).
- Understanding the relationship between αS aggregation and neuroimaging markers in PD is crucial.
Purpose of the Study:
- To investigate the association between CSF SAA results and various radiological measures in PD patients.
- To compare neuroimaging findings between PD patients with and without detectable αS aggregation.
- To explore differences in radiological markers across different PD subtypes (iPD, GBA1-PD, LRRK2-PD).
Main Methods:
- Quantitative radiological measures were obtained from 41 PD patients and 14 healthy controls.
- Measures included striatal binding ratios (SBR), volumetric MRI (whole-brain, deep gray matter), neuromelanin-MRI (NM-MRI), functional connectivity (FC), and white matter diffusion-tensor imaging (DTI).
- Patients were categorized based on SAA results (SAA+ vs. SAA-), with a focus on LRRK2-PD patients.
Main Results:
- PD patients with detectable αS aggregation (PD-SAA+) exhibited reduced whole-brain gray matter, putamenal, brainstem, and substantia nigra volumes.
- PD-SAA+ patients also showed reduced functional connectivity in the left caudate and lower fractional anisotropy in the left fronto-occipital fasciculus compared to PD-SAA- patients.
- αS aggregation was detected in idiopathic PD (iPD), GBA1-PD, and 38% of LRRK2-PD patients, with associated neuroimaging changes.
Conclusions:
- αS aggregation detected by SAA is associated with significant neuroimaging alterations in PD patients.
- These radiological changes, including reduced brain volumes and altered connectivity, appear less pronounced in SAA-negative PD patients.
- The findings suggest that SAA status may reflect the extent of neurodegeneration and potentially disease severity in Parkinson's disease.
