Objective: To test if alpha-synuclein (α-syn) levels in CSF, plasma and saliva predict PD status in the BioFind cohort, and to test whether α-syn levels in different biofluids correlate with each other.

Background: Lower CSF α-syn levels have been found in PD compared to controls in multiple studies. Whether α-syn levels in plasma and saliva predict PD is controversial. In addition, whether α-syn levels in different biofluids correlate with each other has not been examined.

Methods: We compared α-syn concentration between moderately advanced PD and controls in the cross-sectional BioFIND cohort. α-Syn levels were measured in CSF (n, PD= 101, controls = 79), plasma (n, PD= 118, controls = 95) and saliva (n, PD= 22, controls = 26) obtained on the same day.  Differences in concentrations were compared by Student’s t-test. We further tested the association between PD status (outcome) and α-syn concentrations (predictor) in logistic regression models for each medium adjusting for age, gender, and hemoglobin. Lastly, we correlated CSF, plasma and saliva α-syn concentrations. Saliva collection was added later in the study and available in a smaller subset.

Results: (pg/ml): We observed lower α-syn concentration in PD versus controls in CSF (1462.2 versus 1706.4, p=.012) but not in plasma (113023.1 versus 114549.3, p=.890) nor in saliva (285.4 versus 166.0, p=.243). The ability of CSF α-syn concentration to predict PD status was maintained after adjustment for age and gender, in a regression model (OR=.932, 95%CI=.885, .980, p=.006, where .932 is the odds ratio of a PD diagnosis with each 100 pg/ml increase in α-syn). We found a significant association between hemoglobin levels and α-syn in saliva (r=.643, p=.001), a modest one in plasma (r=.210, p=.023), but not in CSF (r=.041, p=.683). There was no correlation between CSF and plasma (r=-.147, p=.143), CSF and saliva (r=.113, p=.636) or plasma and saliva (r=.028, p=.900) α-syn concentrations.

Conclusions: In the BioFIND cohort, a lower CSF α-syn level was associated with PD diagnosis. Plasma measurements of α-syn were not correlated with CSF α-syn, nor were they useful in distinguishing between PD cases and controls. Larger studies of saliva α-syn are required to assess its utility as a biomarker for PD, including consideration of the potential impact by blood contamination.

References: Kang UJ, Goldman JG, Alcalay RN, et al. The BioFIND study: characteristics of a clinically typical Parkinson’s disease biomarker cohort. Mov Disord 2016;31:924-932

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MDS Abstracts - https://www.mdsabstracts.org/abstract/csf-plasma-and-saliva-alpha-synuclein-in-moderately-advanced-parkinsons-disease-cohort-the-biofind-study/