Biochemical markers for severity and risk in GBA and LRRK2 Parkinson's disease

The phenotype of Parkinson's disease (PD) is variable with mutations in genes such as LRRK2 and GBA explaining part of this heterogeneity. Additional genetic and environmental factors contribute to disease variability.

To assess the association between biochemical markers, PD severity and probability score for prodromal PD, among GBA and LRRK2 mutation carriers.

Levels of uric acid, vitamin D, C-reactive protein, microalbumin/creatinine ratio (ACR), white blood count (WBC), hemoglobin, platelets, neutrophil/lymphocyte ratio and estimated glomerular filtration rate (eGFR) were assessed from patients with PD and non-manifesting carriers (NMC) of mutations in GBA and LRRK2, together with disease related questionnaires enabling the construction of the MDS prodromal probability score.

A total of 241 patients with PD: 105 idiopathic PD (iPD), 49 LRRK2-PD and 87 GBA-PD and 412 non-manifesting subjects; 74 LRRK2-NMC, 118 GBA-NMC and 220 non-manifesting non-carriers (NMNC), participated in this study. No significant differences in biochemical measures were detected among patients with PD or non-manifesting carriers. Among GBA-PD patients, worse motor performance was associated with ACR (B = 4.68, 95% CI (1.779-7.559); p = 0.002). The probability score for prodromal PD among all non-manifesting participants was associated with eGFR; NMNC (B = - 0.531 95% CI (- 0.879 to - 0.182); p < 0.001, LRRK2-NMC (B = - 1.014 95% CI (- 1.663 to - 0.366); p < 0.001) and GBA-NMC (B = - 0.686 95% CI (1.300 to - 0.071); p = 0.029).

Sub-clinical renal impairment is associated with increased likelihood for prodromal PD regardless of genetic status. While the mechanism behind this finding needs further elucidation, it suggests that kidney function might play a role in PD pathogenesis.