Insulin resistance, neuroinflammation, and Alzheimer's disease

Rev Neurosci. 2014;25(4):509-25. doi: 10.1515/revneuro-2013-0050.

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.

Publication types

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

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Humans
  • Inflammation / metabolism
  • Insulin / metabolism
  • Insulin Resistance*
  • Signal Transduction

Substances

  • Amyloid beta-Protein Precursor
  • Insulin