Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, The University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada.
Mol Neurobiol. 2018 Jun;55(6):5006-5018. doi: 10.1007/s12035-017-0703-3. Epub 2017 Aug 10.
The majority of Alzheimer's disease (AD) cases are sporadic with unknown causes. Many dietary factors including excessive alcohol intake have been reported to increase the risk to develop AD. The effect of alcohol on cognitive functions and AD pathogenesis remains elusive. In this study, we investigated the relationship between ethanol exposure and Alzheimer's disease. Cell cultures were treated with ethanol at different dosages for different durations up to 48 h and an AD model mouse was fed with ethanol for 4 weeks. We found that ethanol treatment altered amyloid β precursor protein (APP) processing in cells and transgenic AD model mice. High ethanol exposure increased the levels of APP and beta-site APP cleaving enzyme 1 (BACE1) and significantly promoted amyloid β protein (Aβ) production both in vitro and in vivo. The upregulated APP and BACE1 expressions upon ethanol treatment were at least partially due to the activation of APP and BACE1 transcriptions. Furthermore, ethanol treatment increased the deposition of Aβ and neuritic plaque formation in the brains and exuberated learning and memory impairments in transgenic AD model mice. Taken together, our results demonstrate that excessive ethanol intake facilitates AD pathogenesis.
大多数阿尔茨海默病（AD）病例是散发性的，病因不明。许多饮食因素，包括过量饮酒，据报道会增加患 AD 的风险。酒精对认知功能和 AD 发病机制的影响仍不清楚。在这项研究中，我们研究了乙醇暴露与阿尔茨海默病之间的关系。细胞培养物用不同剂量的乙醇处理不同时间，最长达 48 小时，并用乙醇喂养 AD 模型小鼠 4 周。我们发现乙醇处理改变了细胞中淀粉样前体蛋白（APP）的加工和转基因 AD 模型小鼠。高乙醇暴露增加了 APP 和β-位点 APP 切割酶 1（BACE1）的水平，并显著促进了体外和体内的淀粉样β蛋白（Aβ）的产生。乙醇处理后 APP 和 BACE1 的表达上调至少部分归因于 APP 和 BACE1 转录的激活。此外，乙醇处理增加了大脑中 Aβ的沉积和神经突斑块形成，并使转基因 AD 模型小鼠的学习和记忆损伤加重。总之，我们的结果表明，过量饮酒会促进 AD 的发病机制。
