TMEM106B基因多态性与阿尔茨海默病发病的关系及其机制

ASSOCIATION OF TMEM 106 B GENE POLYMORPHISMS WITH THE PATHOGENESIS OF ALZHEIMER’S DISEASE

目的探讨TMEM106B参与阿尔茨海默病(Alzheimer’s disease,AD)发病的可能机制。方法从阿尔茨海默病神经影像学计划(ADNI)研究队列纳入接受TMEM106B rs1990622基因分型和AD脑脊液(CSF)核心蛋白、神经影像学评估的受试者308名,根据CSFβ淀粉样蛋白42(Aβ_(1-42))水平将其分为AD病理组和非AD病理组。收集患者的年龄、性别、受教育年限、基因型、AD CSF核心蛋白[包括Aβ_(1-42)、总tau蛋白(T-tau)和磷酸化tau蛋白(P-tau)]水平及神经影像学指标[包括海马、内嗅皮质及颞叶内侧MRI结果及氟脱氧葡萄糖正电子发射计算机断层扫描(FDG-PET)标准摄入值(SUV)]。采用卡方检验或t检验比较两组受试者上述指标,并采用多因素线性模型分析TMEM106B rs1990622位点多态性与AD关键表型的关联性。结果两两比较结果显示,AD病理组及非AD病理组受试者的Aβ_(1-42)、T-tau、P-tau水平及载脂蛋白E?4携带状态、FDG-PET SUV、各脑区(海马、内侧颞叶和内嗅皮质)体积比较差异有显著性(t=-6.137~50.792,P<0.05)。多因素线性模型分析结果显示,AD病理组女性受试者的TMEM106B rs1990622位点多态性与CSF Aβ_(1-42)水平存在显著关联(β=58.637,t=2.664,P<0.001)。结论TMEM106B rs1990622位点多态性与CSF Aβ_(1-42)水平存在关联,TMEM106B可能是通过影响CSF Aβ_(1-42)代谢参与AD的疾病过程。

Objective To investigate the possible role of TMEM 106 B in Alzheimer’s disease(AD).Methods A total of 308 subjects who were included in the Alzheimer’s disease Neuroimaging Initiative cohort study and underwent TMEM106B rs1990622 genotyping,cerebrospinal fluid(CSF)core protein detection,and neuroimaging measurements were enrolled,and according to the level of CSFβamyloid protein 42(Aβ_(1-42)),they were divided into AD pathological group and non-AD pathological group.Related data were collected,including age,sex,years of education,genotype,levels of CSF core proteins[Aβ_(1-42),total tau(T-tau),and phosphorylated tau(P-tau)],and neuroimaging indicators[MRI results of the hippocampus,the entorhinal cortex,and the medial temporal lobe and standard intake value(SUV)on fluorodeoxyglucose positron emission computed tomography(FDG-PET)].The chi-square test or the t-test was used for comparison of the above indices between the two groups,and the multivariate linear regression model was used to analyze the association of TMEM 106 B rs1990622 polymorphism with the key phenotype of AD.Results A pairwise comparison showed that there were significant differences between the AD pathological group and the non-AD pathological group in the levels of Aβ_(1-42),T-tau,and p-tau,the proportion of patients carrying APOE 4,FGG-PET SUV,and the volume of various brain regions(hippocampus,medial temporal lobe,and entorhinal cortex)(t=-6.137-50.792,P<0.05).The multivariate linear regression model showed that in the female patients in the AD pathological group,TMEM 106B rs1990622 polymorphism was significantly associated with the level of Aβ_(1-42) in CSF(β=58.637,t=2.664,P<0.001).Conclusion TMEM 106 B rs1990622 polymorphism is associated with the level of Aβ_(1-42) in CSF,and TMEM 106 B may be involved in the disease process of AD by affecting the metabolism of CSF Aβ_(1-42).