Abstract: 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.
Keywords: Alzheimer’s disease, amyloid-β, dementia, hyperphosphorylated tau, melatonin, mitochondria dysfunction, oxidative stress, pathogenesis, sex hormones, thyroid hormone, vitamin D
