精准医学杂志 (Aug 2023)
ASSOCIATION OF TMEM106B GENE POLYMORPHISMS WITH THE PATHOGENESIS OF ALZHEIMER’S DISEASE
Abstract
Objective To investigate the possible role of TMEM106B 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 CSF β amyloid protein 42 (Aβ1-42), 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 [Aβ1-42, 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 TMEM106B 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 Aβ1-42, T-tau, and p-tau, the proportion of patients carrying APOE ɛ4, 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, TMEM106B rs1990622 polymorphism was significantly associated with the level of Aβ1-42 in CSF (β=58.637,t=2.664,P<0.001). Conclusion TMEM106B rs1990622 polymorphism is associated with the level of Aβ1-42 in CSF, and TMEM106B may be involved in the disease process of AD by affecting the metabolism of CSF Aβ1-42.
Keywords
