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Elevated α-synuclein and NfL levels in tear fluids and decreased retinal microvascular densities in patients with Parkinson’s disease

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Abstract

The pathognomonic hallmark of Parkinson’s disease (PD), α-synuclein, has been observed in the retina of PD patients. We investigated whether biomarkers in the tears and retinal microvascular changes associate with PD risk and progression. This prospective study enrolled 49 PD patients and 45 age-matched healthy controls. The α-synuclein and neurofilament light chain (NfL) levels were measured using an electrochemiluminescence immunoassay. Retinal vessel density was assessed using optical coherence tomography angiography (OCT-A). The Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Mini-Mental State Examination score were used to assess motor and cognitive progression. The α-synuclein and NfL levels in the tears were higher in PD patients than in controls (α-synuclein: 55.49 ± 8.12 pg/mL vs. 31.71 ± 3.25 pg/mL, P = 0.009; NfL: 2.89 ± 0.52 pg/mL vs. 1.47 ± 0.23 pg/mL, P = 0.02). The vessel densities in the deep plexus of central macula and the radial peripapillary capillary layer of disc region were lower in PD patients with moderate-stage compared with early-stage PD (P < 0.05). The accuracy of predicting PD occurrence using age and sex alone (area under the curve [AUC] 0.612) was significantly improved by adding α-synuclein and NfL levels and retinal vascular densities (AUC 0.752, P = 0.001). After a mean follow-up of 1.5 ± 0.3 years, the accuracy of predicting motor or cognitive progression using age, sex, and baseline motor severity as a basic model was increased by incorporating retinal microvascular and biofluid markers as a full model (P = 0.001). Our results showed that retinal microvascular densities combined with α-synuclein and NfL levels in tears are associated with risk and progression of PD.

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Acknowledgements

The authors thank all the participants in this study. They also thank the staff of the Second Core Laboratory, Department of Medical Research, National Taiwan University Hospital for their technical support of the study.

Funding

The authors are grateful to the funding support from the Academia Sinica (AS-HLGC-110–03) and National Taiwan University Hospital (111-UN0036).

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Authors and Affiliations

  1. Department of Ophthalmology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan

    Chao-Wen Lin

  2. Department of Ophthalmology, En Chu Kong Hospital, New Taipei City, Taiwan

    Tzu-Ting Lai

  3. Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, 100, Taiwan

    Szu-Ju Chen & Chin-Hsien Lin

  4. Department of Neurology, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan

    Szu-Ju Chen

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Contributions

Conceptualization: CW Lin and CH Lin; data curation: CW Lin, TT Lai, SJ Chen, and CH Lin; formal analysis: CW Lin, TT Lai, and SJ Chen; funding acquisition: CH Lin. investigation: CW Lin, TT Lai, and CH Lin; methodology: CW Lin, TT Lai, SJ Chen, and CH Lin; resources: CW Lin, TT Lai, and CH Lin; supervision: CH Lin. validation: CW Lin and CH Lin; writing — original draft: CW Lin; writing — review and editing: CH Lin.

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Correspondence to Chin-Hsien Lin.

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Lin, CW., Lai, TT., Chen, SJ. et al. Elevated α-synuclein and NfL levels in tear fluids and decreased retinal microvascular densities in patients with Parkinson’s disease. GeroScience 44, 1551–1562 (2022). https://doi.org/10.1007/s11357-022-00576-6

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