Wang Xiaoyu, Xiong Yongqin, Duan Caohui, Hu Jianxing, Lu Haoxuan, Yang Mingliang, Huang Jiayu, Li Yan, Li Zhixuan, Wang Song, Wang Miao, Yin Xi, Zhao Jing, Gao Zhongbao, Lou Xin
Department of Radiology, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
School of Medicine, Nankai University, No. 94 Weijin Road, Nankai District, Tianjin, 300071, China.
J Neurol. 2025 Mar 31;272(4):300. doi: 10.1007/s00415-025-13035-x.
Brain structure characteristics form the basis on regulating neuroplastic processes by genes, and structural alterations may contribute to the progression of Parkinson's disease (PD) and their divergent clinical manifestations. However, the neural mechanisms underlying the relations between the genetic signatures to structural alterations in PD patients are unclear. This study aimed to integrate alterations in cortical thickness and subcortical nuclei volume (thalamus, hippocampus, and amygdala) in PD, and to explore global cortical thickness differences associated with gene function. 7-Tesla magnetic resonance imaging scans were obtained for 98 patients with PD and 74 healthy controls (HC). Cortical thickness and subcortical nuclei volume were extracted based on FreeSurfer and were analyzed using general linear model to find significant differences between two groups. Regression model was used for cross-sectional the impact of structural alterations on motor signs as well as non-motor symptoms. Gene-imaging association analysis was used to characterize its gene signatures. Compared with HC, PD patients exhibited the disease-specific structural pattern, characterized by reduced cortical thickness in the right pars triangularis and altered volumes of specific nuclei subfields. Moreover, the Cornu Ammonis 1 head volume was significantly correlated with rigidity scores. Using human brain gene expression data, genes identified in this study were enriched for ribosome and synaptic organization and explain significant variation in global cortical thickness differences. Taken together, these findings may contribute to a better understanding of neural mechanisms in PD and the functional roles of genes that influence brain structure.
脑结构特征构成了基因调节神经可塑性过程的基础,结构改变可能促成帕金森病(PD)的进展及其不同的临床表现。然而,PD患者基因特征与结构改变之间关系的神经机制尚不清楚。本研究旨在整合PD患者皮质厚度和皮质下核体积(丘脑、海马体和杏仁核)的改变,并探索与基因功能相关的全脑皮质厚度差异。对98例PD患者和74名健康对照者(HC)进行了7特斯拉磁共振成像扫描。基于FreeSurfer提取皮质厚度和皮质下核体积,并使用一般线性模型进行分析,以发现两组之间的显著差异。回归模型用于横断面分析结构改变对运动症状以及非运动症状的影响。基因-影像关联分析用于表征其基因特征。与HC相比,PD患者表现出疾病特异性的结构模式,其特征为右侧三角部皮质厚度降低以及特定核亚区体积改变。此外,海马体头部体积与强直评分显著相关。利用人类脑基因表达数据,本研究中鉴定出的基因在核糖体和突触组织方面富集,并解释了全脑皮质厚度差异的显著变化。综上所述,这些发现可能有助于更好地理解PD的神经机制以及影响脑结构的基因的功能作用。