Pathophysiology and Underlying Mechanisms: Pathways to Alzheimer’s Plaque Formation

One of the most common causes of dementia, which is also becoming the biggest burden socially, economically, and from a public health standpoint to any health care system of the planet, currently, is Alzheimer’s disease (AD). It is most commonly characterized by the formation of plaques and neuronal tangles and an increase in phosphorylated tau proteins. The past decade has seen immense development in underlying mechanisms, the discovery of curative or protective genes, and the effect of lifestyle changes in AD. A staggering 55 million cases of dementia associated with AD have been estimated worldwide as per Alzheimer’s Disease International and this number is predicted to increase threefold by the mid of the century. The major risk factors of AD are advanced age and APOE ε4 alleles; females are at a higher risk of developing AD than men; and most cases (60–80%) of AD have been traced back to hereditary roots. PSEN1, PSEN2, APP, SORL1, etc. have shown strong risk incidence, where variants of genes like APP673T, APOE e2, etc. are termed protective variants of AD. This chapter will go in depth through the development, pathophysiology, and underlying genetic variation and alteration that lead to the formation of amyloid plaques, tau phosphorylation, and neuronal tangles.