PDF(Pubmed)
Abstract：
The impact of Alzheimer\'s disease (AD) and its related dementias is rapidly expanding, and its mitigation remains an urgent social and technical challenge. To date there are no effective treatments or interventions for AD, but recent studies suggest that alcohol consumption is correlated with the risk of developing dementia. In this review, we synthesize data from preclinical, clinical, and epidemiological models to evaluate the combined role of alcohol consumption and serotonergic dysfunction in AD, underscoring the need for further research on this topic. We first discuss the limitations inherent to current data-collection methods, and how neuropsychiatric symptoms common among AD, alcohol use disorder, and serotonergic dysfunction may mask their co-occurrence. We additionally describe how excess alcohol consumption may accelerate the development of AD via direct effects on serotonergic function, and we explore the roles of neuroinflammation and proteostasis in mediating the relationship between serotonin, alcohol consumption, and AD. Lastly, we argue for a shift in current research to disentangle the pathogenic effects of alcohol on early-affected brainstem structures in AD.
摘要：
阿尔茨海默病（AD）及其相关痴呆的影响正在迅速扩大，其缓解仍然是一个紧迫的社会和技术挑战。迄今为止，尚无有效的AD治疗或干预措施。但是最近的研究表明，饮酒与患痴呆症的风险有关。在这次审查中,我们从临床前综合数据，临床,和流行病学模型来评估酒精消费和血清素能功能障碍在AD中的联合作用，强调需要对这一主题进行进一步研究。我们首先讨论当前数据收集方法固有的局限性，以及AD中常见的神经精神症状，酒精使用障碍,5-羟色胺能功能障碍可能掩盖了它们的共同发生。我们还描述了过量饮酒如何通过对血清素能功能的直接影响加速AD的发展。我们探讨了神经炎症和蛋白质抑制在介导5-羟色胺之间的关系中的作用，酒精消费,和AD。最后,我们主张在目前的研究中转变为解开酒精对AD早期受影响的脑干结构的致病作用。
