Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, #123, Ta-Pei Road, Niaosung, Kaohsiung, 833, Taiwan.
Psychiatric Department, Taipei Veterans General Hospital, Taipei, Taiwan.
Mol Neurobiol. 2018 Jun;55(6):4637-4649. doi: 10.1007/s12035-017-0668-2. Epub 2017 Jul 13.
The catechol-O-methyltransferase enzyme metabolizes dopamine in the prefrontal axis, and its genetic polymorphism (rs4680; Val158Met) is a known determinant of dopamine signaling. In this study, we investigated the possible structural covariance networks that may be modulated by this functional polymorphism in patients with Alzheimer's disease. Structural covariance networks were constructed by 3D T1 magnetic resonance imaging. The patients were divided into two groups: Met-carriers (n = 91) and Val-homozygotes (n = 101). Seed-based analysis was performed focusing on triple-network models and six striatal networks. Neurobehavioral scores served as the major outcome factors. The role of seed or peak cluster volumes, or a covariance strength showing Met-carriers > Val-homozygotes were tested for the effect on dopamine. Clinically, the Met-carriers had higher mental manipulation and hallucination scores than the Val-homozygotes. The volume-score correlations suggested the significance of the putaminal seed in the Met-carriers and caudate seed in the Val-homozygotes. Only the dorsal-rostral and dorsal-caudal putamen interconnected peak clusters showed covariance strength interactions (Met-carriers > Val-homozygotes), and the peak clusters also correlated with the neurobehavioral scores. Although the triple-network model is important for a diagnosis of Alzheimer's disease, our results validated the role of the dorsal-putaminal-anchored network by the catechol-O-methyltransferase Val158Met polymorphism in predicting the severity of cognitive and behavior in subjects with Alzheimer's disease.
儿茶酚-O-甲基转移酶在额前轴中代谢多巴胺，其遗传多态性（rs4680；Val158Met）是多巴胺信号的已知决定因素。在这项研究中，我们研究了这种功能性多态性可能调节的阿尔茨海默病患者的结构协变网络。结构协变网络是通过 3D T1 磁共振成像构建的。患者分为两组：Met 携带者（n=91）和 Val 纯合子（n=101）。 重点关注三网络模型和六个纹状体网络，进行基于种子的分析。神经行为评分作为主要的结果因素。对种子或峰值簇体积的作用，或表现为 Met 携带者>Val 纯合子的协变强度进行了测试，以了解对多巴胺的影响。临床结果显示，Met 携带者的心理操作和幻觉评分高于 Val 纯合子。体积评分相关性表明，在 Met 携带者中，壳核种子和在 Val 纯合子中，尾状核种子具有重要意义。只有背侧-额侧和背侧-尾侧壳核相互连接的峰值簇显示出协变强度相互作用（Met 携带者>Val 纯合子），并且这些峰值簇与神经行为评分相关。尽管三网络模型对阿尔茨海默病的诊断很重要，但我们的结果通过儿茶酚-O-甲基转移酶 Val158Met 多态性验证了背侧壳核锚定网络在预测阿尔茨海默病患者认知和行为严重程度方面的作用。
