Objective: To investigate the association between cerebrospinal (CSF) αS aggregates, MRI, and dopamine transporter spectral tomography (DaTscan^TM) imaging metrics.

Background: Synuclein amplification assays (SAA) enables the verification of alpha-synuclein (αS) aggregates; a widely considered a pathological hallmark of Parkinson’s disease (PD). Yet, αS aggregation is only detected in ~50% of LRRK2-PD patients.

Method: Forty-two PD patients (14 iPD, 14 GBA-PD, and 14 LRRK2-PD; mean age ±SD = 63.16 ± 9.5 yrs; F/M: 13/29) were included in the final analysis of this study. All participants underwent comprehensive neurological and cognitive assessments, lumbar puncture for CSF collection, DAT-SPECT and MRI scans including diffusion tensor (DT), and resting-state fMRI datasets. Quantitative measures including deep grey matter volumes, diffusion-tensor (DT) indices along white matter (WM) fibers, functional connectivity (FC), and striatal binding ratio (SBR) values were calculated.

Results: Nine (all LRRK2-PD) out of 42 patients were found negative for αS based on SAA (SAA-). No significant differences in demographic variables were detected between SAA+ and SAA- groups. SAA+ PD patients demonstrated significantly reduced FC in the right and left caudate (p=0.002, Bonferroni-corrected). In DTI, SAA– showed significantly lower fractional anisotropy (FA) along the left external capsule (p<0.001, Bonferroni-corrected), and higher FA along the left fronto-occipital fasciculus (SFOF) (p<0.001, Bonferroni-corrected) compared to the SAA+ group.

Conclusion: In PD, αS aggregation is linked to reduced FC in the caudate nucleus, as well as patterns of WM integrity alterations; reflecting the ongoing degenerative pattern that is not observed in a subgroup of SAA- individuals.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/radiological-markers-of-csf-%ce%b1-synuclein-aggregation-in-parkinsons-disease-patients/