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

Scientific paper - Review paper

• Author: Suélen Santos Alves
• Author: Rui Milton Patrício da Silva-Junior
• Author: Gabriel Servilha-Menezes
• Author: Jan Homolak
• Author: Melita Šalković-Petrišić
• Author: Norberto Garcia-Cairasco
• Author's institution: University of Zagreb; School of Medicine; (Department of Pharmacology)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Pharmacology

Abstract (english)

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.

• Keywords (english): Alzheimer Disease / drug therapy; Alzheimer Disease / genetics; Alzheimer Disease / metabolism; Amyloid / genetics; Amyloid / metabolism; Biomarkers; Brain / drug effects; Brain / metabolism; Drug Discovery; Humans; Insulin Resistance / physiology; Models, Biological; tau Proteins / genetics; tau Proteins / metabolism
• Language: english
• Publication type: Scientific paper - Review paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Accepted version
• Journal title: Journal of Alzheimer's Disease
• Numbering: vol. 82, no. 1, pp. 71-105
• p-ISSN: 1387-2877
• e-ISSN: 1875-8908
• DOI: https://doi.org/10.3233/JAD-210234
• URN:NBN: urn:nbn:hr:105:761673
• Publication: 2021
• Document URL: https://www.medra.org/servlet/aliasResolver?alias=iospress&doi=10.3233/JAD-210234
• Type of resource: Text
• Access conditions: Open access
• Created on: 2022-06-27 08:09:15