Validating Tears as a Biomarker in Atypical Presentations of Parkinson Disease: Mark Lew, MD


The director of the Division of Movement Disorders at the USC Keck School of Medicine discussed the efforts needed to validate tears as a biomarker in patients who don’t present with typical Parkinson disease. [WATCH TIME: 4 minutes]

"Our results have been replicated by ourselves in several different populations and we know that there’s a substantial difference in oligomeric alpha-synuclein compared with healthy controls. We’re at a point now where we can look at these atypical syndromes. Had we done that earlier, I don’t think there would have been any validity because our assay was still in its infancy."

In a preliminary study, a group of investigators found significantly elevated levels of oligomeric alpha synuclein in both basal tears and reflex tears in patients with Parkinson disease (PD) vs healthy controls (HCs). Although that study had a homogenous sample related to disease duration, a new analysis evaluated whether the protein composition of reflex tears differs based on disease stage. To do so, reflex tears were collected in 77 early-stage (disease duration, 0-4 years), 43 intermediate-stage (5-8 years), and 50 late-stage PD cases and 67 HCs.1

These protein levels were significantly increased by 5.4-fold in tears of early PD (4.28 [±0.75] ng/mg tear protein; P <.001), 4.0-fold in tears of intermediate PD (3.23 [±0.54] ng/mg tear protein; P <.001), and 3.1-fold in tears of late PD (2.44 [±0.40] ng/mg tear protein; P <.001) relative to HCs (0.80 [±0.24] ng/mg tear protein). The findings indicated that oligomeric synuclein levels in tear fluid do not distinguish the stage of PD.

According to lead investigator Mark Lew, MD, this is the first time that tears have been evaluated as a biomarker for PD, thus prompting the need for further validation. At the 2022 American Academy of Neurology (AAN) Annual Meeting, April 2-7, in Seattle, Washington, Lew, director of the Division of Movement Disorders at the USC Keck School of Medicine, sat down to discuss the next steps needed to expand on these findings. He stressed research looking at atypical presentations of the disease and warned that the field needs to proceed with caution, as this research wades into relatively uncharted waters.

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1. Lew M, Janga S, Ju Y, et al. Biomarkers for Parkinson disease with reflex tears stratified by disease duration. Presented at: 2022 AAN Annual Meeting; April 2-7, Seattle, Washington. Abstract 3750
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