Insulin Resistance as a Common Link Between Current Alzheimer's Disease Hypotheses

Author(s)

Alves, Suelen Santos ^[1] ; Patricio da Silva-Junior, Rui Milton ^{[2, 3]} ; Servilha-Menezes, Gabriel ^[2] ; Homolak, Jan ^{[4, 5]} ; Salkovic-Petrisic, Melita ^{[4, 5]} ; Garcia-Cairasco, Norberto ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo FMRP USP, Dept Neurosci & Behav Sci, Ribeirao Preto Med Sch, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo FMRP USP, Ribeirao Preto Med Sch, Dept Physiol, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo FMRP USP, Dept Internal Med, Ribeirao Preto Med Sch, Ribeirao Preto, SP - Brazil

^[4] Univ Zagreb, Dept Pharmacol, Sch Med, Zagreb - Croatia

^[5] Univ Zagreb, Croatian Inst Brain Res, Sch Med, Zagreb - Croatia

• Document type: Review article
• Source: JOURNAL OF ALZHEIMER'S DISEASE; v. 82, n. 1, p. 71-105, 2021.
• Web of Science Citations: 1

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. (AU)

• FAPESP's process: 19/00849-2 - Uncovering pathophysiological and molecular mechanisms involved in tumorigenesis by platforms for next-generation sequencing (NGS)
• Grantee: Rui Milton Patrício da Silva Junior
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 19/05957-8 - Epilepsies and neuropsyquiatric comorbidities: characterization of the effects of the treatment with cannabidiol and HUF-101 in in vivo and in vitro experimental models
• Grantee: Norberto Garcia Cairasco
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/50891-1 - INCT 2014: Translational Medicine
• Grantee: Jaime Eduardo Cecilio Hallak
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/02787-4 - Effects of cannabidiol vehiculated in nanoemulsion in rats submitted to the chemical model of temporal lobe epilepsy
• Grantee: Gabriel Servilha Menezes
• Support Opportunities: Scholarships in Brazil - Scientific Initiation