Lanore Aymeric, Gaurav Rahul, Lejeune François Xavier, Basset Aymeric, Tesson Christelle, Kodjovi Gatepe, Sambin Sara, Mangone Graziella, Arnulf Isabelle, Vidailhet Marie, Mariani Louise-Laure, Brice Alexis, Lesage Suzanne, Lehericy Stéphane, Corvol Jean-Christophe
Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm 1127, CNRS 7225, Paris, 75013, France.
Assistance Publique Hôpitaux de Paris, NS-Park/FCRIN network, Department of Neurology, CIC Neurosciences, Hôpital Pitié-Salpêtrière, Paris, 75013, France.
Brain. 2025 May 16. doi: 10.1093/brain/awaf184.
Parkinson's disease is characterized by the degeneration of dopaminergic neurons in the substantia nigra, and neuromelanin-sensitive MRI provides a biomarker to track this neuronal loss. Isolated rapid eye movement sleep behavior disorder, associated with cognitive decline, may represent a distinct subtype of synucleinopathy. Polygenic risk scores for these conditions may be associated with the neuronal degeneration. This study investigates whether genetic risk scores for Parkinson's disease (PGS000903) or isolated rapid eye movement sleep behavior disorder (PGS003414) are associated with neuromelanin signal loss in the substantia nigra in the ICEBERG cohort. The analysis included 123 individuals with Parkinson's disease, 37 with isolated rapid eye movement sleep behavior disorder, and 48 healthy individuals. Neuromelanin signal intensity was analyzed through linear mixed models by status and genetic risk adjusted for age and sex. Compared to healthy controls, patients with Parkinson's disease had higher genetic risk scores for both disorders, while patients with isolated rapid eye movement sleep behavior disorder had higher genetic risk scores only for rapid eye movement sleep behavior disorder. Both patient groups showed significant signal loss over time (P<0.001). In Parkinson's disease, higher genetic risk for the condition was associated with greater neuromelanine signal decline (P=0.008), particularly in sensorimotor (P=0.04) and limbic (P=0.02) regions. No significant association was found in isolated rapid eye movement sleep behavior disorder. In Parkinson's disease, genetic susceptibility was linked to neuromelanin signal loss, indicating genetic susceptibility to neuronal degeneration. The absence of significant effect in isolated rapid eye movement sleep behavior disorder may be due to a lack of power. These results should be replicated in independent studies.
帕金森病的特征是黑质中多巴胺能神经元的退化，而神经黑色素敏感的磁共振成像提供了一种生物标志物来追踪这种神经元损失。与认知衰退相关的孤立性快速眼动睡眠行为障碍可能代表了一种独特的突触核蛋白病亚型。这些疾病的多基因风险评分可能与神经元退化有关。本研究调查帕金森病（PGS000903）或孤立性快速眼动睡眠行为障碍（PGS003414）的遗传风险评分是否与ICEBERG队列中黑质的神经黑色素信号损失相关。分析包括123名帕金森病患者、37名孤立性快速眼动睡眠行为障碍患者和48名健康个体。通过线性混合模型，根据年龄和性别调整状态和遗传风险，分析神经黑色素信号强度。与健康对照相比，帕金森病患者在这两种疾病中的遗传风险评分更高，而孤立性快速眼动睡眠行为障碍患者仅在快速眼动睡眠行为障碍方面有更高的遗传风险评分。两组患者随着时间的推移均出现了显著的信号损失（P<0.0）。在帕金森病中，该疾病的较高遗传风险与更大的神经黑色素信号下降相关（P=0.008），特别是在感觉运动区（P=0.04）和边缘区（P=0.02）。在孤立性快速眼动睡眠行为障碍中未发现显著关联。在帕金森病中，遗传易感性与神经黑色素信号损失有关，表明对神经元退化具有遗传易感性。在孤立性快速眼动睡眠行为障碍中未发现显著影响可能是由于样本量不足。这些结果应在独立研究中进行重复验证。
