神经退行性变
淀粉样前体蛋白
多态性(计算机科学)
基因
淀粉样蛋白(真菌学)
阿尔茨海默病
医学
神经科学
遗传学
生物
内科学
内分泌学
疾病
基因型
病理
作者
Hang-Rai Kim,Taeyeop Lee,Jung Choi,Yong Jeong
出处
期刊:Alzheimer Disease & Associated Disorders
[Ovid Technologies (Wolters Kluwer)]
日期:2020-12-14
卷期号:35 (2): 114-120
被引量:3
标识
DOI:10.1097/wad.0000000000000422
摘要
Introduction A weak association between amyloid β (Aβ) deposition and neurodegeneration biomarkers, such as brain atrophy, has been repeatedly reported in a subset of patients with Alzheimer disease, suggesting individual differences in response to Aβ deposition. Methods Here, we performed a genome-wide interaction study to identify single-nucleotide polymorphism (SNP) that modify the effect of Aβ (measured by F-florbetapir positron emission tomography) on brain atrophy (measured by cortical thickness using magnetic resonance imaging). We used magnetic resonance imaging, positron emission tomography, cerebrospinal fluid, and genetic data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database [discovery cohort, ADNI-GO/2 (n=723) and replication cohort, ADNI-1 (n=129)]. Results We identified a genome-wide suggestive interaction of rs3807779 SNP (β=-0.14, SE=0.029, P=9.08×10) in the discovery cohort. The greater dosage of rs3807779 SNP increased the detrimental effect of Aβ deposition on cortical thickness. In replication analyses, the congruent results were replicated to confirm our findings. Furthermore, rs3807779 SNP augmented the detrimental effect of Aβ deposition on cognitive function. Genetic profiling showed that rs3807779 has chromatin interactions with the promoter region of MAGI2 gene, suggesting its association with MAGI2 expression. Conclusions These findings demonstrate that subjects carrying the rs3807779 SNP are more susceptible to Aβ-related neurodegeneration.
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