Understanding the link between insulin resistance and Alzheimer's disease: Insights from animal models

Natalia de M Lyra E Silva; Rafaella Araujo Gonçalves; Susan E Boehnke; Leticia Forny-Germano; Douglas P Munoz; Fernanda G De Felice

doi:10.1016/j.expneurol.2019.03.016

Understanding the link between insulin resistance and Alzheimer's disease: Insights from animal models

Exp Neurol. 2019 Jun:316:1-11. doi: 10.1016/j.expneurol.2019.03.016. Epub 2019 Mar 28.

Authors

Natalia de M Lyra E Silva¹, Rafaella Araujo Gonçalves¹, Susan E Boehnke¹, Leticia Forny-Germano², Douglas P Munoz³, Fernanda G De Felice⁴

Affiliations

¹ Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada.
² Institute of Medical Biochemistry Leopoldo De Meis, Federal University of Rio de Janeiro, Brazil.
³ Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada. Electronic address: doug.munoz@queensu.ca.
⁴ Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada; Department of Psychiatry, Queen's University, Kingston, ON, Canada; Institute of Medical Biochemistry Leopoldo De Meis, Federal University of Rio de Janeiro, Brazil. Electronic address: fernanda.defelice@queensu.ca.

PMID: 30930096
DOI: 10.1016/j.expneurol.2019.03.016

Abstract

Alzheimer's disease (AD) is a devastating neurodegenerative disease affecting millions of people worldwide. AD is characterized by a profound impairment of higher cognitive functions and still lacks any effective disease-modifying treatment. Defective insulin signaling has been implicated in AD pathophysiology, but the mechanisms underlying this process are not fully understood. Here, we review the molecular mechanisms underlying defective brain insulin signaling in rodent models of AD, and in a non-human primate (NHP) model of the disease that recapitulates features observed in AD brains. We further highlight similarities between the NHP and human brains and discuss why NHP models of AD are important to understand disease mechanisms and to improve the translation of effective therapies to humans. We discuss how studies using different animal models have contributed to elucidate the link between insulin resistance and AD.

Keywords: Alzheimer’s disease; Animal models; Cognitive control; Inflammation; Insulin; Insulin resistance.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Alzheimer Disease / pathology*
Animals
Humans
Insulin Resistance*
Models, Animal