Objective: To determine if the protein composition of reflex tears differs in Parkinson’s disease (PD) patients stratified by disease duration compared to Healthy Controls (HC).

Background: We have previously shown that oligomeric alpha synuclein is significantly elevated in both basal tears (anesthetized Schirmer´s test) and reflex tears (unanesthetized Schirmer´s test) in PD patients versus HC. Our patient sample was homogeneous related to disease duration. We have designed this study to evaluate the efficacy of collecting reflex tears to provide a true biomarker capable of differentiating PD progression compared to HC.

Method: Reflex tears were collected from 57 male and female early disease duration (0-4 years) 34 intermediate (5-8 years), and 37 late disease duration (greater than 9 years) PD patients and 55 male and female HC using an unanesthetized Schirmer´s test. Samples were pooled from both eyes for analysis of oligomeric alpha-synuclein. Values were measured by ELISA and normalized to protein content of the sample. (Detailed methods described in refs below)’

Results: Oligomeric alpha-synuclein was significantly increased by 9.0-fold in tears of early PD patients (4.52 ± 0.92 ng/mg tear protein, p-value< 0.001 ), 5.7-fold in tears of intermediate PD (2.85 ± 0.61 ng/mg tear protein, p-value< 0.001) and 3.7 fold in tears of late PD (2.1 ± 0.47 ng/mg tear protein, p-value<0.01) relative to HC (0.50 ± 0.12 ng/mg tear protein). No significant sex differences were present.

Conclusion: Oligomeric alpha-synuclein levels in tear fluid may enable discrimination between various stages of PD patients based on disease duration compared to HC. The current study is conducted in an independent cohort compared to our previous studies and the results 1) validate previous findings that oligomeric alpha-synuclein levels are increased in reflex tears of PD patients compared to HC; and 2) suggest that elevations in oligomeric alpha-synuclein are more pronounced in patients with early stage than late stage PD.

References: Sarah F Hamm-Alvarez, Curtis T Okamoto, Srikanth R Janga, Danielle Feigenbaum, Maria C Edman, Daniel Freire, Mihir Shah, Raveena Ghanshani, Wendy J Mack, Mark F Lew. Oligomeric α-Synuclein Is Increased in Basal Tears of Parkinson’s Patients. Biomark Med , 13 (11), 941-952 Aug 2019 Sarah F Hamm-Alvarez, Srikanth R Janga, Maria C Edman, Danielle Feigenbaum, Daniel Freire, Wendy J Mack, Curtis T Okamoto , Mark F Lew Levels of Oligomeric α-Synuclein in Reflex Tears Distinguish Parkinson’s Disease Patients From Healthy Controls.Biomark Med, 13 (17), 1447-1457 Dec 2019

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MDS Abstracts - https://www.mdsabstracts.org/abstract/biomarkers-for-parkinsons-disease-with-reflex-tears-correlate-with-disease-duration/