MAPT and Mental deterioration: In 1984, Aβ was identified as the primary component of extracellular amyloid plaques in AD,1 which is the unique pathological hallmark of the disease.53 Hardy and Higgins then proposed “the amyloid cascade hypothesis” in 1992, positing that Aβ deposits in the brain are the initiating event of AD pathogenesis, resulting in subsequent tau tangle formation, neuronal loss and dysfunction as well as cognitive decline.2 Since then, many genetic and non-genetic studies have supported this hypothesis.