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Research Paper|Volume 12, Issue 2|pp 1488—1495

Plasma ubiquitin C-terminal hydrolase L1 levels reflect disease stage and motor severity in Parkinson’s disease

Adeline Su Lyn Ng1,2, Yi Jayne Tan1, Zhonghao Lu1, Ebonne Yulin Ng3, Samuel Yong Ern Ng1, Nicole Shuang Yu Chia1, Fiona Setiawan3, Zheyu Xu1, Nicole Chwee Har Keong2,4, Kay Yaw Tay1, Wing Lok Au1, Louis Chew Seng Tan1, Eng-King Tan2,3
  • 1Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital, 308433, Singapore
  • 2Neuroscience and Behavioural Disorders Program, Duke-NUS Medical School, 169857, Singapore
  • 3Department of Neurology, National Neuroscience Institute, Singapore General Hospital, 169856, Singapore
  • 4Department of Neurosurgery, National Neuroscience Institute, Tan Tock Seng Hospital, 308433, Singapore
* Equal contribution
Received: October 22, 2019Accepted: December 25, 2019Published: January 13, 2020
https://doi.org/10.18632/aging.102695

Copyright: © 2020 Ng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Parkinson’s disease (PD) is characterized by Lewy bodies containing α-synuclein and ubiquitin aggregates, their co-occurrence possibly linked to a failure of the ubiquitin proteasome system. Ubiquitin C-terminal hydrolase L1 (UCHL1) plays an important role in maintenance of nervous system integrity, and overexpression of UCHL1 has been shown to increase ubiquitin levels within neurons. While cerebrospinal fluid ubiquitin levels were reported to be lower in PD vs controls, plasma UCHL1 levels and their relationship with clinical measures in PD has not been reported. We measured plasma UCHL1 levels using single molecule array (Simoa) in 291 subjects (242 PD and 49 healthy controls, HC). We found that UCHL1 levels were significantly higher in PD patients at moderate stages (Hoehn and Yahr, H&Y stage >2) vs milder PD (H&Y ≤2, p<0.001) and HC (p=0.001). There was no significant difference in UCHL1 levels between PD patients at H&Y stages ≤2 vs HC. Across all PD patients, UCHL1 correlated significantly with UPDRS Part III motor scores (β=3.87, 95% CI=0.43-7.31, p=0.028), but not with global cognition. Overall, we found that UCHL1 correlates with motor function in PD, with higher levels seen in later disease stages. These findings will be validated in longitudinal studies.