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Licensed Unlicensed Requires Authentication Published by De Gruyter March 13, 2014

Insulin resistance, neuroinflammation, and Alzheimer’s disease

  • Dema Najem , Michelle Bamji-Mirza , Nina Chang , Qing Yan Liu and Wandong Zhang EMAIL logo

Abstract

Alzheimer’s disease (AD) is the most common form of dementia. Pathologically, it is characterized by degeneration of neurons and synapses, the deposition of extracellular plaques consisting of aggregated amyloid-β (Aβ) peptides, and intracellular neurofibrillary tangles made up of hyperphosphorylated tau protein. Recently, the spotlights have been centered on two characteristics of AD, neuroinflammation and insulin resistance. Because both of these pathways play roles in synaptic dysfunction and neurodegeneration, they become potential targets for therapeutic intervention that could impede the progression of the disease. Here, we present an overview of the traditional amyloid hypothesis, as well as emerging data on both inflammatory and impaired insulin signaling pathways in AD. It becomes evident that more than one concurrent treatment can be synergistic and various combinations should be discussed as a potential therapeutic strategy to correct the anomalies in AD. Insulin resistance, Aβ/tau pathologies, neuroinflammation, and dysregulation of central nervous system homeostasis are intertwined processes that together create the complex pathology of AD and should be considered as a whole picture.


Corresponding author: Wandong Zhang, Faculty of Medicine, University of Ottawa, Ottawa K1H 8M5, Canada, e-mail: and Human Health Therapeutics, National Research Council Canada, 1200 Montreal Road, Ottawa K1A 0R6, Canada

Acknowledgements

This work is supported by CIHR grants (CIHR 106886 & TAD 125698) to W.Z. and an Ontario Graduate Scholarship, an admission scholarship, and an excellence scholarship from the University of Ottawa to D.N.

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Received: 2013-11-5
Accepted: 2014-2-13
Published Online: 2014-3-13
Published in Print: 2014-8-1

© 2014 by De Gruyter

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