Inflammation and Insulin Resistance as Risk Factors and Potential Therapeutic Targets for Alzheimer's Disease

Angeles Vinuesa, Carlos Pomilio, Amal Gregosa, Melisa Bentivegna, Jessica Presa, Melina Bellotto, Flavia Saravia, Juan Beauquis, Angeles Vinuesa, Carlos Pomilio, Amal Gregosa, Melisa Bentivegna, Jessica Presa, Melina Bellotto, Flavia Saravia, Juan Beauquis

Abstract

Overnutrition and modern diets containing high proportions of saturated fat are among the major factors contributing to a low-grade state of inflammation, hyperglycemia and dyslipidemia. In the last decades, the global rise of type 2 diabetes and obesity prevalence has elicited a great interest in understanding how changes in metabolic function lead to an increased risk for premature brain aging and the development of neurodegenerative disorders such as Alzheimer's disease (AD). Cognitive impairment and decreased neurogenic capacity could be a consequence of metabolic disturbances. In these scenarios, the interplay between inflammation and insulin resistance could represent a potential therapeutic target to prevent or ameliorate neurodegeneration and cognitive impairment. The present review aims to provide an update on the impact of metabolic stress pathways on AD with a focus on inflammation and insulin resistance as risk factors and therapeutic targets.

Keywords: Alzheimer’s disease; cognitive impairment; inflammation; insulin resistance; metabolic disorders; therapies.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Vinuesa, Pomilio, Gregosa, Bentivegna, Presa, Bellotto, Saravia and Beauquis.

Figures

FIGURE 1
FIGURE 1
Shared pathophysiological pathways and synergic burden of obesity-related disorders and Alzheimer’s disease.
FIGURE 2
FIGURE 2
Schematic representation of interacting components of the insulin signaling and inflammatory pathways on the brain. Pointed-head arrows depict activation and blunt-end arrows inhibition, while letter circles A-I point the level at which the potential therapeutic approaches discussed in this article would act. Treatment definition and corresponding reference section are defined in the inferior square.

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