Modeling Alzheimer's disease: from past to future

Alzheimer's disease (AD) is emerging as the most prevalent and socially disruptive illness of aging populations, as more people live long enough to become affected. Although AD is placing a considerable and increasing burden on society, it represents the largest unmet medical need in neurology, because current drugs improve symptoms, but do not have profound disease-modifying effects. Although AD pathogenesis is multifaceted and difficult to pinpoint, genetic and cell biological studies led to the amyloid hypothesis, which posits that amyloid \u3b2 (A\u3b2) plays a pivotal role in AD pathogenesis. Amyloid precursor protein (APP), as well as \u3b2- and \u3b3-secretases are the principal players involved in A\u3b2 production, while \u3b1-secretase cleavage on APP prevents A\u3b2 deposition. The association of early onset familial AD with mutations in the APP and \u3b3-secretase components provided a potential tool of generating animal models of the disease. However, a model that recapitulates all the aspects of AD has not yet been produced. Here, we face the problem of modeling AD pathology describing several models, which have played a major role in defining critical disease-related mechanisms and in exploring novel potential therapeutic approaches. In particular, we will provide an extensive overview on the distinct features and pros and contras of different AD models, ranging from invertebrate to rodent models and finally dealing with computational models and induced pluripotent stem cells