BackgroundDifferences in cortical morphology have been reported in individuals with Parkinson's disease (PD). However, the pathophysiological mechanism of transcriptomic vulnerability in local brain regions remains unclear.ObjectiveThis study aimed to characterize the morphometric changes of brain regions in early drug‐naive PD patients and uncover the brain‐wide gene expression correlates.MethodsThe morphometric similarity (MS) network analysis was used to quantify the interregional structural similarity from multiple magnetic resonance imaging anatomical indices measured in each brain region of 170 early drug‐naive PD patients and 123 controls. Then, we applied partial least squares regression to determine the relationship between regional changes in MS and spatial transcriptional signatures from the Allen Human Brain Atlas dataset, and identified the specific genes related to MS differences in PD. We further investigated the biological processes by which the PD‐related genes were enriched and the cellular characterization of these genes.ResultsOur results showed that MS was mainly decreased in cingulate, frontal, and temporal cortical areas and increased in parietal and occipital cortical areas in early drug‐naive PD patients. In addition, genes whose expression patterns were associated with regional MS changes in PD were involved in astrocytes, excitatory, and inhibitory neurons and were functionally enriched in neuron‐specific biological processes related to trans‐synaptic signaling and nervous system development.ConclusionsThese findings advance our understanding of the microscale genetic and cellular mechanisms driving macroscale morphological abnormalities in early drug‐naive PD patients and provide potential targets for future therapeutic trials.

中文翻译：

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初治帕金森病的形态相似性差异与转录组特征相关

背景据报道，帕金森病 (PD) 患者的皮质形态存在差异。然而，局部脑区转录组脆弱性的病理生理机制仍不清楚。目的本研究旨在表征早期初治帕金森病患者脑区的形态变化，揭示全脑基因表达的相关性。方法形态相似性（MS）网络该分析用于量化 170 名早期未接受药物治疗的 PD 患者和 123 名对照者每个大脑区域的多个磁共振成像解剖指标的区域间结构相似性。然后，我们应用偏最小二乘回归来确定 MS 的区域变化与 Allen Human Brain Atlas 数据集中的空间转录特征之间的关系，并确定了与 PD 中 MS 差异相关的特定基因。我们进一步研究了PD相关基因富集的生物过程以及这些基因的细胞特征。结果我们的结果表明，早期MS主要在扣带皮层、额叶和颞叶皮层区域减少，而在顶叶和枕叶皮层区域增加。未接受药物治疗的 PD 患者。此外，表达模式与 PD 局部 MS 变化相关的基因涉及星形胶质细胞、兴奋性和抑制性神经元，并且在与跨突触信号传导和神经系统发育相关的神经元特异性生物过程中功能丰富。结论这些发现推进了我们的研究。了解导致早期未用药帕金森病患者宏观形态异常的微观遗传和细胞机制，并为未来的治疗试验提供潜在目标。