The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory
The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory
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DOI：
10.1038/s41467-019-09564-5
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发表时间：
2019-04-16
影响因子：
16.6
通讯作者：
Simpson, Donna M.
中科院分区：
文献类型：
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作者：
Franzmeier, Nicolai;Rubinski, Anna;Simpson, Donna M.
桥接整合子 1 基因 (BIN1) 中的单核苷酸多态性 (SNP) rs744373 是阿尔茨海默病 (AD) 的危险因素。在大脑中，BIN1 参与胞吞作用并维持细胞骨架的完整性。尸检和体外研究表明，BIN1 相关的 AD 风险是由 tau 病理增加介导的，但 rs744373 是否与体内 tau 病理增加相关尚不清楚。在这里，我们在 89 名没有痴呆症的老年人中发现，BIN1 rs744373 风险等位基因携带者在对应于 Braak II-VI 期的大脑区域显示出更高的 AV1451 tau-PET。相反，BIN1 rs744373 SNP 与 AV45 淀粉样蛋白-PET 摄取无关。此外，rs744373 风险等位基因与较差的记忆表现相关，这是由整体 tau 水平升高介导的。总之，我们的研究结果表明，BIN1 rs744373 SNP 与 tau 蛋白升高相关，但与 β-淀粉样蛋白病理学无关，这表明 BIN1 的改变可能通过 tau 蛋白病理学升高导致记忆缺陷。
The single nucleotide polymorphism (SNP) rs744373 in the bridging integrator-1 gene (BIN1) is a risk factor for Alzheimer's disease (AD). In the brain, BIN1 is involved in endocytosis and sustaining cytoskeleton integrity. Post-mortem and in vitro studies suggest that BIN1-associated AD risk is mediated by increased tau pathology but whether rs744373 is associated with increased tau pathology in vivo is unknown. Here we find in 89 older individuals without dementia, that BIN1 rs744373 risk-allele carriers show higher AV1451 tau-PET across brain regions corresponding to Braak stages II-VI. In contrast, the BIN1 rs744373 SNP was not associated with AV45 amyloid-PET uptake. Furthermore, the rs744373 risk-allele was associated with worse memory performance, mediated by increased global tau levels. Together, our findings suggest that the BIN1 rs744373 SNP is associated with increased tau but not beta-amyloid pathology, suggesting that alterations in BIN1 may contribute to memory deficits via increased tau pathology.