Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 82, Issue 1, Pages 71-105Publisher
IOS PRESS
DOI: 10.3233/JAD-210234
Keywords
Alzheimer's disease; biomarkers; insulin resistance; memory; metabolism
Categories
Funding
- Sao Paulo Research Foundation - FAPESP [17/211 55-3, 19/02787-4, 19/05957-8, 19/00849-2]
- National Institutes for Science and Technology (INCT) - Translational Medicine, FAPESP [14/50891-1]
- National Council for Scientific and Technological Development (CNPq) [465458/2014-9]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior Brasil (CAPES) [001]
- CNPq [305883/2014-3]
- Coordenadoria de Aperfeicoamento de Pessoal de Nivel Superior - PROEX-CAPES
- CNPq Research Fellowship
- Croatian Science Foundation [IP-2018-01-8938]
- Scientific Center of Excellence for Basic, Clinical and Translational Neuroscience (Project Experimental and clinical research of hypoxic-ischemic damage in perinatal and adult brain
- European Union through the European Regional Development Fund [GA KK01.1.1.01.0007]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [19/02787-4, 19/05957-8, 19/00849-2, 14/50891-1] Funding Source: FAPESP
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Alzheimer's disease is a severe public health problem and current medical approaches are limited to symptomatic interventions, with a high failure rate in clinical trials. While most studies have focused on the amyloid cascade hypothesis, it is clear that AD is a multifactorial disorder.
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.
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