Objective: To assess the association between α-synuclein seed amplification assay (α-synuclein SAA) status with the supportive criteria of the MDS Clinical Diagnostic Criteria for Parkinson’s disease (PD).

Background: Abnormal α-synuclein aggregation can be detected through α-synuclein SAA. It seems to be present in most people with PD which makes it a promising biomarker for PD. However, the association between pathological α-synuclein and diagnostic features of PD is not fully understood.

Method: This cross-sectional study included individuals with PD and completed α-synuclein SAA (n=1,066) enrolled in the Parkinson Progression Marker Initiative (PPMI) which is a longitudinal, observational, international, multicentre study. We used the motor examination and motor complication sections of the MDS Unified Parkinson’s Disease Rating Scale (MDS-UPDRS-III and IV, respectively) and University of Pennsylvania Smell Identification Test (UPSIT) to evaluate each of the supportive criteria from the MDS Clinical Diagnostic Criteria for PD. Individuals with deep brain stimulation were excluded when assessing L-dopa responsiveness and L-dopa induced dyskinesias. Logistical regression models were created to calculate odds ratios and 95% confidence intervals. The models were adjusted for age and sex.

Results: We found 927 (87%) participants who had a positive α-synuclein SAA. Out of these, 692 individuals were treated with dopaminergic medication and had on/off MDS-UPDRS-III assessments completed. L-dopa responsiveness was associated with a positive α-synuclein SAA (OR 1.74; 95% CI 1.07-2.83). 829 individuals taking dopaminergic medication had MDS-UPDRS-IV completed. L-dopa induced dyskinesias were associated with a positive α-synuclein SAA (OR 2.17; 95% CI 1.34-3.51). Rest tremor was associated with a positive α-synuclein SAA (OR 1.76; 95% CI 1.21-2.55). 218 individuals had completed an UPSIT, 84% were found to be hyposmic. Olfactory loss was associated with positive α-synuclein SAA (OR 19.01; 95% CI 7.13-50.71).

Conclusion: This study shows that α-synuclein SAA positivity seems to be associated with all MDS supportive criteria for PD. Limitations of this study include incomplete capture of clinical features by the UPDRS assessment and missing data, particularly in UPSIT assessments. Future work to analyse PD phenotypes and disease progression in relation to α-synuclein SAA status would be of interest.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/mds-clinical-supportive-criteria-for-parkinsons-disease-are-associated-with-%ce%b1-synuclein-seed-amplification-assay-status/