Fan Liyuan, Mao Chengyuan, Hu Xinchao, Zhang Shuo, Yang Zhihua, Hu Zhengwei, Sun Huifang, Fan Yu, Dong Yali, Yang Jing, Shi Changhe, Xu Yuming
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
Front Neurol. 2020 Jan 10;10:1312. doi: 10.3389/fneur.2019.01312. eCollection 2019.
Alzheimer's disease (AD), a common neurodegenerative disease in the elderly and the most prevalent cause of dementia, is characterized by progressive cognitive impairment. The prevalence of AD continues to increase worldwide, becoming a great healthcare challenge of the twenty-first century. In the more than 110 years since AD was discovered, many related pathogenic mechanisms have been proposed, and the most recognized hypotheses are the amyloid and tau hypotheses. However, almost all clinical trials targeting these mechanisms have not identified any effective methods to treat AD. Scientists are gradually moving away from the simple assumption, as proposed in the original amyloid hypothesis, to new theories of pathogenesis, including gamma oscillations, prion transmission, cerebral vasoconstriction, growth hormone secretagogue receptor 1α (GHSR1α)-mediated mechanism, and infection. To place these findings in context, we first reviewed the neuropathology of AD and further discussed new insights in the pathogenesis of AD.
阿尔茨海默病(AD)是老年人常见的神经退行性疾病,也是痴呆最常见的病因,其特征为进行性认知障碍。AD在全球的患病率持续上升,成为21世纪重大的医疗保健挑战。自AD被发现的110多年来,人们提出了许多相关的致病机制,其中最被认可的假说是淀粉样蛋白假说和tau蛋白假说。然而,几乎所有针对这些机制的临床试验都未找到治疗AD的有效方法。科学家们正逐渐摒弃最初淀粉样蛋白假说中提出的简单假设,转而研究新的发病机制理论,包括γ振荡、朊病毒传播、脑血管收缩、生长激素促分泌素受体1α(GHSR1α)介导的机制以及感染。为了更好地理解这些发现,我们首先回顾了AD的神经病理学,并进一步探讨了AD发病机制的新见解。