Catechol-O-Methyltransferase Val158Met Polymorphism on Striatum Structural Covariance Networks in Alzheimer's Disease

被引:5
作者
Chang, Chiung-Chih [1 ]
Tsai, Shih-Jen [2 ,3 ]
Chen, Nai-Ching [1 ]
Huang, Chi-Wei [1 ]
Hsu, Shih-Wei [4 ]
Chang, Ya-Ting [1 ]
Liu, Mu-En [2 ]
Chang, Wen-Neng [1 ]
Tsai, Wan-Chen [1 ]
Lee, Chen-Chang [4 ]
机构
[1] Chang Gung Univ, Coll Med, Kaohsiung Chang Gung Mem Hosp, Dept Neurol,Cognit & Aging Ctr, 123 Ta Pei Rd, Kaohsiung 833, Taiwan
[2] Taipei Vet Gen Hosp, Psychiat Dept, Taipei, Taiwan
[3] Natl Yang Ming Univ, Sch Med, Psychiat Div, Taipei, Taiwan
[4] Chang Gung Univ, Coll Med, Kaohsiung Chang Gung Mem Hosp, Dept Radiol, Kaohsiung, Taiwan
关键词
Alzheimer's disease; Anatomical structural covariance; Default mode network; Genetic effect; Striatal network; Posterior cingulate cortex; DEFAULT-MODE NETWORK; BASAL-GANGLIA; RHESUS-MONKEY; FRONTOTEMPORAL DEMENTIA; BEHAVIORAL VARIANT; COGNITIVE FUNCTION; PREFRONTAL CORTEX; DORSAL STRIATUM; PROJECTIONS; CONNECTIVITY;
D O I
10.1007/s12035-017-0668-2
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:4637 / 4649
页数:13
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