Movement Disorder Unit, Laboratory of Early Markers of Neurodegeneration, Neurological Institute, Tel-Aviv Medical Center, 6 Weizmann Street, 64239, Tel-Aviv, Israel.
Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel.
J Neurol. 2021 Apr;268(4):1517-1525. doi: 10.1007/s00415-020-10325-4. Epub 2021 Jan 3.
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.
帕金森病（PD）的表型具有变异性，LRRK2 和 GBA 等基因突变解释了这种异质性的一部分。其他遗传和环境因素也促成了疾病变异性。
评估 GBA 和 LRRK2 突变携带者中生化标志物、PD 严重程度和前驱 PD 概率评分之间的关系。
从患有 PD 的患者和 GBA 和 LRRK2 突变的非显性携带者（NMC）中评估尿酸、维生素 D、C 反应蛋白、微量白蛋白/肌酐比（ACR）、白细胞计数（WBC）、血红蛋白、血小板、中性粒细胞/淋巴细胞比值和估计肾小球滤过率（eGFR）的水平，同时使用疾病相关问卷构建 MDS 前驱概率评分。
共纳入 241 名 PD 患者：105 名特发性 PD（iPD）、49 名 LRRK2-PD 和 87 名 GBA-PD 以及 412 名非显性受试者；74 名 LRRK2-NMC、118 名 GBA-NMC 和 220 名非显性非携带者（NMNC）参与了这项研究。PD 患者或非显性携带者之间的生化指标无显著差异。在 GBA-PD 患者中，较差的运动表现与 ACR 相关（B=4.68，95%CI（1.779-7.559）；p=0.002）。所有非显性参与者的前驱 PD 概率评分与 eGFR 相关；NMNC（B=-0.531，95%CI（-0.879 至-0.182）；p<0.001）、LRRK2-NMC（B=-1.014，95%CI（-1.663 至-0.366）；p<0.001）和 GBA-NMC（B=-0.686，95%CI（1.300 至-0.071）；p=0.029）。
亚临床肾功能损害与前驱 PD 的可能性增加有关，无论遗传状态如何。虽然这一发现背后的机制尚需进一步阐明，但它表明肾功能可能在 PD 发病机制中发挥作用。
