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Association of Total Bilirubin with Motor Signs in Early Parkinson’s Disease in LRRK2 Variant Carriers

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Abstract

Oxidative stress is considered a possible mechanism in Parkinson’s disease (PD) progression. Bilirubin has been recognized as a powerful antioxidant that increases due to heme-oxygenase activity. We aimed to investigate the association of total bilirubin (TB) with motor signs and asymmetry in different stages of early PD. A case–control study was performed to investigate the differences in TB levels in PD patients and healthy controls (HC) both carrying LRRK2 variants. We compared TB levels in HC and Hoehn and Yahr (HY) I and II cohorts separately, followed by multiple linear regression analysis to evaluate the association between TB and motor dysfunction in each stage. We used Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (UPDRS) part III scores and asymmetry scores to address motor disability. Asymmetry scores were calculated from the corresponding UPDRS III tasks. TB was significantly increased in HY II compared to HC (P < 0.001). Positive correlations with TB were found for UPDRS III total score (ρ = 0.303, P = 0.034) and asymmetry score (ρ = 0.418, P = 0.003) in HY I. Multiple linear regression found a significant relationship between TB and asymmetry scores in HY I (R2 = 0.261, P = 0.037), but no relationship was achieved with UPDRS III total scores. Increased TB serves as an important diagnostic marker in earlier stages of PD. A significant relationship was found between TB and motor asymmetry in HY I patients. According to our findings, bilirubin mainly exhibits its protective effects in HY I population.

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Data Availability Statement 

The data used in this research was obtained from PPMI and is available with permission to all researchers.

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Acknowledgements

PPMI—a public–private partnership—is funded by the Michael J. Fox Foundation for Parkinson’s Research and funding partners. Full names of all of the PPMI funding partners can be found at www.ppmi-info.org/about-ppmi/who-we-are/study-sponsors.

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DK contributed to conceptualization, data curation, drafting manuscript, and development of methodology. HH contributed to conceptualization, data curation, and drafting manuscript. ASC revised and edited the manuscript. All authors reviewed and approved the final manuscript.

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Correspondence to Danial Kazemi.

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Statement of Ethics

This study was conducted using PPMI data. The PPMI study is ethically approved and conducted in accordance with the Declaration of Helsinki, 1964.

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The ethical approval of PPMI is available at ClinicalTrials.gov with Identifier: NCT01141023.

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Written informed consent was obtained from the participants.

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The authors declare no competing interests.

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Kazemi, D., Hajishah, H. & Chadeganipour, A.S. Association of Total Bilirubin with Motor Signs in Early Parkinson’s Disease in LRRK2 Variant Carriers. J Mol Neurosci 72, 2338–2344 (2022). https://doi.org/10.1007/s12031-022-02067-x

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  • DOI: https://doi.org/10.1007/s12031-022-02067-x

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