Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Feodor-Lynen Straße 17, 81377, Munich, Germany.
Nat Commun. 2019 Apr 16;10(1):1766. doi: 10.1038/s41467-019-09564-5.
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.
单核苷酸多态性 (SNP) rs744373 位于桥连整合因子-1 基因 (BIN1) 中，是阿尔茨海默病 (AD) 的风险因素。在大脑中，BIN1 参与内吞作用和维持细胞骨架完整性。尸检和体外研究表明，BIN1 相关的 AD 风险是由增加的 tau 病理学介导的，但 rs744373 是否与体内增加的 tau 病理学相关尚不清楚。在这里，我们在 89 名没有痴呆的老年人中发现，BIN1 rs744373 风险等位基因携带者在大脑区域的 AV1451 tau-PET 显示出更高的水平，这些区域与 Braak 阶段 II-VI 相对应。相比之下，BIN1 rs744373 SNP 与 AV45 淀粉样蛋白-PET 摄取无关。此外，rs744373 风险等位基因与记忆表现更差相关，这是由全球 tau 水平升高介导的。总之，我们的研究结果表明，BIN1 rs744373 SNP 与 tau 但与 beta-淀粉样蛋白病理学相关，表明 BIN1 的改变可能通过增加 tau 病理学导致记忆缺陷。
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