{"title":"使用神经黑色素敏感成像将多基因风险评分与多巴胺能神经元损失联系起来。","authors":"Aymeric Lanore, Rahul Gaurav, François-Xavier Lejeune, Aymeric Basset, Christelle Tesson, Gatepe Cedoine Kodjovi, Sara Sambin, Graziella Mangone, Isabelle Arnulf, Marie Vidailhet, Louise-Laure Mariani, Alexis Brice, Suzanne Lesage, Stephane Lehericy, Jean-Christophe Corvol","doi":"10.1093/brain/awaf184","DOIUrl":null,"url":null,"abstract":"<p><p>Parkinson's disease is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), and neuromelanin-sensitive MRI provides a biomarker to track this neuronal loss. Isolated REM sleep behaviour disorder (iRBD), associated with cognitive decline, may represent a distinct subtype of synucleinopathy. Polygenic risk scores for these conditions may be associated with neuronal degeneration. This study investigates whether genetic risk scores for Parkinson's disease (PGS000903) or iRBD (PGS003414) are associated with neuromelanin signal loss in the SNc in the ICEBERG cohort. The analysis included 123 individuals with Parkinson's disease, 37 with iRBD and 48 healthy individuals. Neuromelanin signal intensity was analysed through linear mixed models by status and genetic risk, adjusted for age and sex. Compared with healthy controls, patients with Parkinson's disease had higher genetic risk scores for both disorders, while patients with iRBD had higher genetic risk scores only for RBD. 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 neuromelanin signal decline (P = 0.008), particularly in sensorimotor (P = 0.04) and limbic (P = 0.02) regions. No significant association was found in iRBD. In Parkinson's disease, genetic susceptibility was linked to neuromelanin signal loss, indicating genetic susceptibility to neuronal degeneration. The absence of a significant effect in iRBD may be due to a lack of power. These results should be replicated in independent studies.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"3095-3101"},"PeriodicalIF":11.7000,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Linking polygenic risk scores to dopaminergic neuron loss using neuromelanin-sensitive imaging.\",\"authors\":\"Aymeric Lanore, Rahul Gaurav, François-Xavier Lejeune, Aymeric Basset, Christelle Tesson, Gatepe Cedoine Kodjovi, Sara Sambin, Graziella Mangone, Isabelle Arnulf, Marie Vidailhet, Louise-Laure Mariani, Alexis Brice, Suzanne Lesage, Stephane Lehericy, Jean-Christophe Corvol\",\"doi\":\"10.1093/brain/awaf184\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Parkinson's disease is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), and neuromelanin-sensitive MRI provides a biomarker to track this neuronal loss. Isolated REM sleep behaviour disorder (iRBD), associated with cognitive decline, may represent a distinct subtype of synucleinopathy. Polygenic risk scores for these conditions may be associated with neuronal degeneration. This study investigates whether genetic risk scores for Parkinson's disease (PGS000903) or iRBD (PGS003414) are associated with neuromelanin signal loss in the SNc in the ICEBERG cohort. The analysis included 123 individuals with Parkinson's disease, 37 with iRBD and 48 healthy individuals. Neuromelanin signal intensity was analysed through linear mixed models by status and genetic risk, adjusted for age and sex. Compared with healthy controls, patients with Parkinson's disease had higher genetic risk scores for both disorders, while patients with iRBD had higher genetic risk scores only for RBD. 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 neuromelanin signal decline (P = 0.008), particularly in sensorimotor (P = 0.04) and limbic (P = 0.02) regions. No significant association was found in iRBD. In Parkinson's disease, genetic susceptibility was linked to neuromelanin signal loss, indicating genetic susceptibility to neuronal degeneration. The absence of a significant effect in iRBD may be due to a lack of power. These results should be replicated in independent studies.</p>\",\"PeriodicalId\":9063,\"journal\":{\"name\":\"Brain\",\"volume\":\" \",\"pages\":\"3095-3101\"},\"PeriodicalIF\":11.7000,\"publicationDate\":\"2025-09-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Brain\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/brain/awaf184\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/brain/awaf184","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Linking polygenic risk scores to dopaminergic neuron loss using neuromelanin-sensitive imaging.
Parkinson's disease is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), and neuromelanin-sensitive MRI provides a biomarker to track this neuronal loss. Isolated REM sleep behaviour disorder (iRBD), associated with cognitive decline, may represent a distinct subtype of synucleinopathy. Polygenic risk scores for these conditions may be associated with neuronal degeneration. This study investigates whether genetic risk scores for Parkinson's disease (PGS000903) or iRBD (PGS003414) are associated with neuromelanin signal loss in the SNc in the ICEBERG cohort. The analysis included 123 individuals with Parkinson's disease, 37 with iRBD and 48 healthy individuals. Neuromelanin signal intensity was analysed through linear mixed models by status and genetic risk, adjusted for age and sex. Compared with healthy controls, patients with Parkinson's disease had higher genetic risk scores for both disorders, while patients with iRBD had higher genetic risk scores only for RBD. 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 neuromelanin signal decline (P = 0.008), particularly in sensorimotor (P = 0.04) and limbic (P = 0.02) regions. No significant association was found in iRBD. In Parkinson's disease, genetic susceptibility was linked to neuromelanin signal loss, indicating genetic susceptibility to neuronal degeneration. The absence of a significant effect in iRBD may be due to a lack of power. These results should be replicated in independent studies.
期刊介绍:
Brain, a journal focused on clinical neurology and translational neuroscience, has been publishing landmark papers since 1878. The journal aims to expand its scope by including studies that shed light on disease mechanisms and conducting innovative clinical trials for brain disorders. With a wide range of topics covered, the Editorial Board represents the international readership and diverse coverage of the journal. Accepted articles are promptly posted online, typically within a few weeks of acceptance. As of 2022, Brain holds an impressive impact factor of 14.5, according to the Journal Citation Reports.