Associations Between TREML2 Gene Variants and Alzheimer’s Disease: Biomarkers, Neuroimage, and Cognition

阿尔茨海默病神经影像学倡议 SNP公司 肿瘤科 神经影像学 萎缩 大脑大小 大脑结构与功能 心理学 疾病 痴呆 单核苷酸多态性 内科学 医学 生物 基因型 神经科学 遗传学 基因 磁共振成像 放射科
作者
Jieqiong Li,Xiaoling Zhong,Jinghui Song,Song Chi,Anmu Xie,Lan Tan,Jin‐Tai Yu
出处
期刊:Journal of Alzheimer's Disease [IOS Press]
卷期号:96 (4): 1555-1563
标识
DOI:10.3233/jad-230936
摘要

Background: Recent genetic research identified a protective factor against late-onset Alzheimer’s disease (AD) in Caucasians, a variant called rs3747742-C in the TREML2 gene. However, the roles of other TREML2 variants in AD have not been fully explored. Objective: We conducted a focused analysis of 16 TREML2 variants, examining their connection to AD by studying their correlation with cerebrospinal fluid (CSF) proteins, neuroimage, and cognition in the Alzheimer’s Disease Neuroimaging Initiative database (ADNI). Methods: A multiple linear regression model was utilized to estimate potential associations between TREML2 genotypes and various endophenotypes in the entire ADNI sample at baseline, with age, gender, years of education, and APOE ɛ4 status included as covariates. To examine changes in clinical outcomes over time, linear mixed-effects models were employed. Results: We found that the SNP rs17328707-A was associated with higher ADNI-VS scores, smaller ventricles, and larger middle temporal volume at baseline. The SNP rs6915083-G was linked to lower CSF t-tau and p-tau levels, and higher CSF Aβ levels. The SNP rs9394766-G was associated with a smaller hippocampus and larger ventricles at baseline. In longitudinal cohorts, the rs6915083-G SNP was associated with changes in ADNI-MEM and ADNI-EF scores, as well as the rate of hippocampal and middle temporal atrophy. Conclusion: Our findings reveal that TREML2 gene variants have different effects on AD. Two variants are protective, while one may be a risk factor. This enhances our understanding of AD genetics and could guide future research and personalized treatments.
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