Johns Hopkins University.
J Alzheimers Dis. 2019;68(2):417-437. doi: 10.3233/JAD-181052.
Alzheimers' disease (AD) is the most common cause of dementia, with an estimated 5 million new cases occurring annually. Among the elderly, AD shortens life expectancy, results in disability, decreases quality of life, and ultimately, leads to institutionalization. Despite extensive research in the last few decades, its heterogeneous pathophysiology and etiopathogenesis have made it difficult to develop an effective treatment and prevention strategy. Aging is the biggest risk factor for AD and evidence suggest that the total number of older people in the population is going to increase astronomically in the next decades. Also, there is evidence that air pollution and increasing income inequality may result in higher incidence and prevalence of AD. This makes the need for a comprehensive understanding of the etiopathogenesis and pathophysiology of the disease extremely critical. In this paper, a quintuple framework of thyroid dysfunction, vitamin D deficiency, sex hormones, and mitochondria dysfunction and oxidative stress are used to provide a comprehensive description of AD etiopathogenesis and pathophysiology. The individual role of each factor, their synergistic and genetic interactions, as well as the limitations of the framework are discussed.
阿尔茨海默病（AD）是痴呆症最常见的病因，每年估计有 500 万例新发病例。在老年人中，AD 会缩短预期寿命，导致残疾，降低生活质量，最终导致住院治疗。尽管在过去几十年中进行了广泛的研究，但 AD 的异质性病理生理学和病因发病机制使其难以制定有效的治疗和预防策略。衰老是 AD 的最大风险因素，有证据表明，在未来几十年，人口中老年人的总数将呈指数级增长。此外，有证据表明，空气污染和收入不平等加剧可能导致 AD 的发病率和患病率上升。这使得人们对该疾病的病因发病机制和病理生理学有一个全面的了解变得至关重要。在本文中，使用甲状腺功能障碍、维生素 D 缺乏、性激素、线粒体功能障碍和氧化应激的五重框架，对 AD 的病因发病机制和病理生理学进行全面描述。讨论了每个因素的单独作用、它们的协同和遗传相互作用以及该框架的局限性。
