Category: Parkinson's Disease: Genetics
Objective: We measured serum peroxiredoxin-3 (PRDX3) levels in Parkinson’s disease (PD) patients with and without LRRK2 risk variants, hypothesizing that PD LRRK2 carriers will show lower PRDX3 levels compared to PD non-carriers and healthy controls (HC).
Background: Leucine rich repeat kinase 2 (LRRK2) is known to interact with PRDX3, a mitochondrial member of the antioxidant family of thioredoxin (Trx) peroxidases. Mutations in the LRRK2 kinase domain increase phosphorylation of PRDX3, leading to decreased peroxidase activity and increased LRRK2-expressing neuronal cell death. Post-mortem brain samples from PD patients overall show lower PRX3 levels, with corresponding increased phosphorylated PRDX3 levels compared to control brain. Whether this is seen in carriers of Asian LRRK2 PD risk variants (G2385R and R1628P) remain unknown.
Method: Serum PRDX3 levels were measured in 213 cases (45 PD LRRK2 carriers, 104 PD LRRK2 non-carriers, and 64 HC) using ELISA. Global cognitive function was assessed using MMSE and MoCA; motor function was assessed using MDS-UPDRS. Group-wise effects were analysed using ANOVA followed by Bonferroni posthoc analysis. Correlations were determined using Pearson’s correlation coefficient.
Results: Serum PRDX3 levels showed no significant difference between total PD (LRRK2 carriers and non-carriers) vs HC (p=0.214). However, within groups, serum PRDX3 levels were significantly reduced in PD LRRK2 carriers vs PD LRRK2 non-carriers (p<0.001, controlling for age, gender and disease duration), and HC (p=0.001, controlling for age and gender). PRDX3 levels showed no significant correlation with global cognition, Hoehn and Yahr, and UPDRS Motor scores.
Conclusion: Serum PRDX3 levels are significantly reduced in PD patients carrying the Asian LRRK2 risk variants, compared to PD non-carriers and HC, similar to what is seen in LRRK2 G2019S mutation carriers. These findings support the effect of LRRK2 mutations on PRDX3 and highlight the potential for serum PRDX3 as a biomarker for LRRK2 carrier status. Further studies with larger cohorts are needed to validate these findings.
To cite this abstract in AMA style:YJ. Tan, ZH. Lu, EYL. Ng, SYE. Ng, NSY. Chia, ACW. Yong, XY. Choi, DD. Heng, S. Neo, ZY. Xu, KY. Tay, WL. Au, LCS. Tan, EK. Tan, ASL. Ng. Reduced serum PRDX3 levels are a biomarker for Asian LRRK2 carriers in Parkinson’s disease [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/reduced-serum-prdx3-levels-are-a-biomarker-for-asian-lrrk2-carriers-in-parkinsons-disease/. Accessed December 7, 2023.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/reduced-serum-prdx3-levels-are-a-biomarker-for-asian-lrrk2-carriers-in-parkinsons-disease/