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
- 1 Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital, 308433, Singapore
- 2 Neuroscience and Behavioural Disorders Program, Duke-NUS Medical School, 169857, Singapore
- 3 Department of Neurology, National Neuroscience Institute, Singapore General Hospital, 169856, Singapore
- 4 Department of Neurosurgery, National Neuroscience Institute, Tan Tock Seng Hospital, 308433, Singapore
received: October 22, 2019 ; accepted: December 25, 2019 ; published: January 13, 2020 ;https://doi.org/10.18632/aging.102695
How to Cite
Copyright © 2020 Ng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.