Affiliations: [a] Department of Neurosciences and Behavioral Sciences, Ribeirão Preto Medical School - University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil
| [b] Department of Internal Medicine, Ribeirão Preto Medical School –University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil
| [c] Department of Pharmacology, University of Zagreb School of Medicine, Zagreb, Croatia
| [d] Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia
| [e] Department of Physiology, Ribeirão Preto Medical School – University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil
Correspondence:
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Correspondence to: Norberto Garcia-Cairasco, PhD, Department of Physiology, Ribeirão Preto Medical School –University of São Paulo, Av. Dos Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil. E-mail: ngcairas@usp.br.
Abstract: Almost 115 years ago, Alois Alzheimer described Alzheimer’s disease (AD) for the first time. Since then, many hypotheses have been proposed. However, AD remains a severe health public problem. The current medical approaches for AD are limited to symptomatic interventions and the complexity of this disease has led to a failure rate of approximately 99.6%in AD clinical trials. In fact, no new drug has been approved for AD treatment since 2003. These failures indicate that we are failing in mimicking this disease in experimental models. Although most studies have focused on the amyloid cascade hypothesis of AD, the literature has made clear that AD is rather a multifactorial disorder. Therefore, the persistence in a single theory has resulted in lost opportunities. In this review, we aim to present the striking points of the long scientific path followed since the description of the first AD case and the main AD hypotheses discussed over the last decades. We also propose insulin resistance as a common link between many other hypotheses.
