Center for Movement Disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
China National Clinical Research Center for Neurological Diseases, Beijing, China.
Mov Disord. 2023 May;38(5):764-773. doi: 10.1002/mds.29356. Epub 2023 Feb 16.
Pathogenic variants in the glucocerebrosidase gene (GBA) have been identified as the most common genetic risk factor for Parkinson's disease (PD). However, the features of substantia nigra damage in GBA pathogenic variant carriers remain unclear.
We aimed to evaluate the microstructural changes in the substantia nigra in non-manifesting GBA pathogenic variant carriers (GBA-NMC) and PD patients with GBA pathogenic variant (GBA-PD) with free-water imaging.
First, we compared free water values in the posterior substantia nigra between non-manifesting non-carriers (NMNC, n = 29), GBA-NMC (n = 26), and GBA-PD (n = 16). Then, free water values in the posterior substantia nigra were compared between GBA-PD and early- (n = 19) and late-onset (n = 40) idiopathic PD (iPD) patients. Furthermore, we examined whether the baseline free water values could predict the progressions of clinical symptoms.
The free water values in the posterior substantia nigra were significantly higher in the GBA-NMC and GBA-PD groups compared to NMNC, and were significantly increased in the GBA-PD group than both early- and late-onset iPD. Free water values in the posterior substantia nigra could predict the progression of anxiety and cognitive decline in GBA-NMC and GBA-PD groups.
We demonstrate that free water values are elevated in the substantia nigra and predict the development of non-motor symptoms in GBA-NMC and GBA-PD. Our findings demonstrate that a significant nigral impairment already exists in GBA-NMC, and nigral injury may be more severe in GBA-PD than in iPD. These results support that free-water imaging can as a potential early marker of substantia nigra damage. © 2023 International Parkinson and Movement Disorder Society.
糖脑苷脂酶基因（GBA）中的致病性变异已被确定为帕金森病（PD）的最常见遗传风险因素。然而，GBA 致病性变异携带者黑质损伤的特征尚不清楚。
我们旨在使用自由水成像评估非显性 GBA 致病性变异携带者（GBA-NMC）和 GBA 致病性变异 PD 患者黑质的微观结构变化。
首先，我们比较了非显性非携带者（NMNC，n=29）、GBA-NMC（n=26）和 GBA-PD（n=16）的后黑质自由水值。然后，比较了 GBA-PD 与早发性（n=19）和晚发性（n=40）特发性 PD（iPD）患者的后黑质自由水值。此外，我们还检查了基线自由水值是否可以预测临床症状的进展。
GBA-NMC 和 GBA-PD 组的后黑质自由水值明显高于 NMNC，GBA-PD 组明显高于早发性和晚发性 iPD。后黑质自由水值可预测 GBA-NMC 和 GBA-PD 组焦虑和认知能力下降的进展。
我们证明黑质中的自由水值升高，并预测 GBA-NMC 和 GBA-PD 中非运动症状的发展。我们的发现表明，GBA-NMC 中已经存在明显的黑质损伤，并且与 iPD 相比，GBA-PD 中的黑质损伤可能更严重。这些结果支持自由水成像可以作为黑质损伤的潜在早期标志物。© 2023 国际帕金森病和运动障碍协会。
