Serum Uric Acid in LRRK2 Related Parkinson’s Disease: Longitudinal Data from the PPMI Study

Article type: Research Article

Authors: Bougea, Anastasia^a | Koros, Christos^{a; b} | Papagiannakis, Nikolaos^a | Simitsi, Athina-Maria^a | Prentakis, Andreas^{a; c} | Papadimitriou, Dimitra^d | Pachi, Ioanna^{a; b} | Antonelou, Roubina^b | Angelopoulou, Efthalia^a | Beratis, Ion^a | Bozi, Maria^b | Papageorgiou, Sokratis G.^a | Trapali, Xenia Geronicola^c | Stamelou, Maria^{a; e; f} | Stefanis, Leonidas^{a; *}

Affiliations: [a] 1st Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece | [b] 2nd Department of Neurology, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece | [c] Nuclear Medicine Unit, Attikon Hospital, Athens, Greece | [d] Neurology Clinic, Henry Dunan Hospital, Athens, Greece | [e] Neurology Clinic, Philipps University, Marburg, Germany | [f] Parkinson’s disease and Movement Disorders Department, HYGEIA Hospital, Athens, Greece

Correspondence: [*] Correspondence to: Leonidas Stefanis, MD, PhD, 1st Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece and Center of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Vasilisis Sofias 72 str, 11528 Athens, Greece. Tel.: +30 210 728 9405; Fax: +30 210 725 7621; E-mail: lstefanis@bioacademy.gr.

Abstract: Background:Previous studies have highlighted serum uric acid as a putative idiopathic Parkinson’s disease (iPD) biomarker. Only one study, so far, showed higher levels of serum uric acid in leucine-rich repeat kinase 2 (LRRK + 2) carriers compared to those who developed PD, however a longitudinal comparison between LRRK2 + PD and healthy controls (HC) has not been performed. Objective:The aim of this study was to determine whether there are longitudinal differences in serum uric acid between iPD, LRRK2 + PD and HC and their association with motor and non-motor features. Methods:Longitudinal data of uric acid of 282 de novo iPD, 144 LRRK2 + PD patients, and 195 age-matched HC were obtained from the Parkinson’s Progression Markers Initiative (PPMI) database. We also used longitudinal Montreal Cognitive Assessment (MoCA), Movement Disorder Society–Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS-III), Geriatric Depression Scale (GDS) scores, and DaTSCAN striatal binding ratios (SBRs). Results:Longitudinal uric acid measurements were significantly lower in LRRK2 + PD patients compared to HC up to 5 years follow-up. There was no significant impact or correlation of adjusted or unadjusted uric acid levels with MoCA, MDS-UPDRS III, or GDS scores, the presence of RBD or DAT-SCAN SBRs. Conclusion:LRRK2 + PD group had significantly lower uric acid concentrations compared to HC after adjusting for age, sex and baseline BMI up to 5 years follow-up. There were no significant associations between uric acid levels and indices of disease severity. These findings identify serum uric acid as a marker linked to LRRK2 + PD.

Keywords: Leucine rich repeat kinase 2, LRRK2, Parkinson’s disease, Parkinson’s progression markers initiative, montreal cognitive assessment, movement disorder society–unified Parkinson’s disease rating scale part III

DOI: 10.3233/JPD-202337

Journal: Journal of Parkinson's Disease, vol. 11, no. 2, pp. 633-640, 2021