Vo Andrew, Tremblay Christina, Rahayel Shady, Al-Bachari Sarah, Berendse Henk W, Bright Joanna K, Cendes Fernando, d'Angremont Emile, Dalrymple-Alford John C, Debove Ines, Dirkx Michiel F, Druzgal Jason, Garraux Gaëtan, Helmich Rick C, Hu Michele, Jahanshad Neda, Johansson Martin E, Klein Johannes C, Laansma Max A, McMillan Corey T, Melzer Tracy R, Misic Bratislav, Mosley Philip, Owens-Walton Conor, Parkes Laura M, Pellicano Clelia, Piras Fabrizio, Poston Kathleen L, Rango Mario, Rummel Christian, Schwingenschuh Petra, Suette Melanie, Thompson Paul M, Tosun Duygu, Tsai Chih-Chien, van Balkom Tim D, van den Heuvel Odile A, van der Werf Ysbrand D, van Heese Eva M, Vriend Chris, Wang Jiun-Jie, Wiest Roland, Yasuda Clarissa, Dagher Alain
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada.
Department of Medicine, Centre for Advanced Research in Sleep Medicine, University of Montreal, Montreal, Canada.
medRxiv. 2025 May 29:2025.05.25.25326586. doi: 10.1101/2025.05.25.25326586.
Parkinson's disease (PD) is associated with extensive structural brain changes. Recent work has proposed that the spatial pattern of disease pathology is shaped by both network spread and local vulnerability. However, only few studies assessed these biological frameworks in large patient samples across disease stages. Analyzing the largest imaging cohort in PD to date (N = 3,096 patients), we investigated the roles of network architecture and local brain features by relating regional abnormality maps to normative profiles of connectivity, intrinsic networks, cytoarchitectonics, neurotransmitter receptor densities, and gene expression. We found widespread cortical and subcortical atrophy in PD to be associated with advancing disease stage, longer time since diagnosis, and poorer global cognition. Structural brain connectivity best explained cortical atrophy patterns in PD and across disease stages. These patterns were robust among individual patients. The precuneus, lateral temporal cortex, and amygdala were identified as likely network-based epicentres, with high convergence across disease stages. Individual epicentres varied significantly among patients, yet they consistently localized to the default mode and limbic networks. Furthermore, we showed that regional overexpression of genes implicated in synaptic structure and signalling conferred increased susceptibility to brain atrophy in PD. In summary, this study demonstrates in a well-powered sample that structural brain abnormalities in PD across disease stages and within individual patients are influenced by both network spread and local vulnerability.
帕金森病（PD）与广泛的脑结构改变有关。最近的研究提出，疾病病理的空间模式是由网络传播和局部易损性共同塑造的。然而，只有少数研究在跨越疾病阶段的大量患者样本中评估了这些生物学框架。通过分析迄今为止帕金森病领域最大的影像学队列（N = 3096例患者），我们通过将区域异常图谱与连通性、内在网络、细胞构筑学、神经递质受体密度和基因表达的规范图谱相关联，研究了网络结构和局部脑特征的作用。我们发现，帕金森病中广泛的皮质和皮质下萎缩与疾病进展、诊断后时间延长以及整体认知能力较差有关。脑结构连通性最能解释帕金森病及不同疾病阶段的皮质萎缩模式。这些模式在个体患者中具有稳健性。楔前叶、颞叶外侧皮质和杏仁核被确定为可能基于网络的中心，在不同疾病阶段具有高度的汇聚性。个体中心在患者之间有显著差异，但它们始终定位于默认模式和边缘网络。此外，我们表明，与突触结构和信号传导相关的基因的区域过表达使帕金森病患者脑萎缩的易感性增加。总之，这项研究在一个样本量充足的研究中表明，帕金森病在不同疾病阶段和个体患者中的脑结构异常受到网络传播和局部易损性的共同影响。
