Serum uric acid level as a putative biomarker in Parkinson's disease patients carrying GBA1 mutations: 2-Year data from the PPMI study

Abstract

Blood uric acid represents an important biomarker in sporadic Parkinson's disease (PD). Whether uric acid levels change in genetic forms of PD is beginning to be assessed. The aim of the present study was to evaluate differences in serum uric acid level among PD patients harboring mutations in the glucocerebrosidase (GBA1) gene, sporadic PD, and healthy controls followed longitudinally. Methods: Longitudinal 2-year serum uric acid measurement data of 120 GBA-PD patients have been downloaded from the Parkinson's Progression Markers Initiative (PPMI) database. This cohort was compared with 369 de novo sporadic PD patients and 195 healthy controls enrolled in the same study. Results: Following adjustment for age, sex and BMI the GBA-PD cohort exhibited lower 2-year longitudinal uric acid level as compared to the controls (p = 0.016). Baseline uric acid measurements showed only a marginal difference (p = 0.119), but year 2 uric acid levels were lower in the GBA-PD cohort (p < 0.001). There was no difference in baseline, year 2 and 2-year longitudinal serum uric acid in the GBA-PD cohort as compared to sporadic PD (p = 0.664, p = 0.117 and p = 0.315). Conclusions: This is the first study to assess serum uric acid in a GBA-PD cohort. Our findings suggest that low serum uric acid might be a progression biomarker in GBA-PD. However, more studies (ideally longitudinal) on the association between low serum uric acid and clinical data in GBA-PD are needed. These results are consistent with data from previous reports assessing uric acid as a biomarker in other genetic forms of PD.

Serum Uric Acid Levels in Parkinson’s Disease: A Cross-Sectional Electronic Medical Record Database Study from a Tertiary Referral Centre in Romania

“…Interestingly, higher levels of serum UA are associated with a higher risk of developing PD in carriers of pathologic variants of the leucine-rich repeat kinase 2 (LRRK2) gene, the most common cause of familial PD [59], and these patients have lower levels of serum UA compared to healthy controls [60]. A significant association was also found between lower serum UA levels and the GBA1 mutation PD [61].…”

The glucocerebrosidase mutations and uric acid levels in Parkinson’s disease: A 3-years investigation of a potential biomarker”

“…It is found that homozygote mutations of GBA can cause Gaucher disease, while heterozygous vectors are at risk for developing PD [9] . In previous studies, GBA1 mutation was associated with early-onset, the relatively symmetrical onset of limb symptoms, and faster motor and cognitive impairment progression in PD patients; however, the association between different GBA mutation subtypes are less studied [10] , [11] . It is noteworthy that former research has suggested that variants of GBA could be associated with faster progression of motor symptoms, accompanied by accelerated conversion to cognitive impairment and dementia.…”

Machine learning-based prediction of cognitive outcomes in de novo Parkinson's disease

“…Ratios of each measure were also included as independent predictive variables. Total serum uric acid was also included as previously described 37 .…”