Objective: To determine the association between subregional DAT binding ratios (SBRs) for disease risk, PD progression, and whether these associations differ based on SAA status.

Background: Seed amplification assay (SAA) from different tissues enabled to detect this pathology in-vivo. However, the relationship between SAA+ and dopaminergic degeneration, disease risk among “at risk” individuals, remain unclear. Subregional DAT-SPECT dopaminergic quantification may assist in addressing these issues.

Method: DAT-SPECT imaging was performed in a discovery cohort (N=123) including manifest PD (N=45), non-manifesting carriers (NMCs) of PD-related mutations (N=42), and healthy controls (N=34). SBR was quantified in eight striatal subregions at two timepoints. Associations were tested between baseline SBR, annualized SBR change (ΔSBR), probability scores for prodromal PD, and clinical scores stratified by SAA status. Key findings were evaluated in an independent validation cohort (PD N=15; NMC N=13).

Results: In prodromal individuals, lower baseline SBR in the right posterior caudate was associated with higher LR risk scores (p<0.05), indicating early dopaminergic involvement prior to clinical diagnosis. In PD, longitudinal analyses revealed accelerated SBR decline (Δ) in SAA+ individuals, particularly in the anterior putamen. In this subgroup, change in right anterior putamen SBR significantly predicted follow-up MDS-UPDRS motor and total scores (β =0.59 p<0.001 and p=0.002 respectively), independent of age. In contrast, SAA-negative PD showed no consistent coupling between dopaminergic decline and clinical progression. In the validation cohort, right anterior putamen SBR was negatively associated with MDS-UPDRS-III scores (β=−0.65, p=0.042) and MDS-UPDRS total (β=−0.76, p<0.001) in PD. Among NMCs, right posterior putamen SBR correlated with motor scores and was significantly lower in SAA-positive compared with SAA-negative individuals (p=0.047).

Conclusion: Early alterations in posterior striatal regions are associated with prodromal risk, while anterior putamen degeneration relates to clinical progression in PD, particularly among SAA-positive individuals. These findings highlight the value of subregional DAT measures for early detection, biological stratification, and monitoring of disease progression.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/disparate-subregional-striatal-dat-spect-associations-with-csf-synucleinopathy-status-and-clinical-severity-across-parkinsons-disease-continuum/