Metabolic Syndrome as a Risk Factor for Alzheimer's Disease: Is Aβ a Crucial Factor in Both Pathologies?

Antioxid Redox Signal. 2017 Apr 1;26(10):542-560. doi: 10.1089/ars.2016.6768. Epub 2016 Aug 16.

Abstract

Significance: Recently, chronic degenerative diseases have become one of the main health problems worldwide. That is the case of Alzheimer's disease (AD) and metabolic syndrome (MetS), whose expression can be influenced by different risk factors. Recent Advances: In recent decades, it has been widely described that MetS increases the risk of cognitive impairment and dementia. MetS pathogenesis involves several vascular risk factors such as diabetes, dyslipidemia, hypertension, and insulin resistance (I/R).

Critical issues: Reported evidence shows that vascular risk factors are associated with AD, particularly in the development of protein aggregation, inflammation, oxidative stress, neuronal dysfunction, and disturbances in signaling pathways, with insulin receptor signaling being a common alteration between MetS and AD.

Future directions: Insulin signaling has been involved in tau phosphorylation and amyloid β (Aβ) metabolism. However, it has also been demonstrated that Aβ oligomers can bind to insulin receptors, triggering their internalization, decreasing neuron responsiveness to insulin, and promoting insulin I/R. Thus, it could be argued that Aβ could be a convergent factor in the development of both pathologies. Antioxid. Redox Signal. 26, 542-560.

Keywords: Alzheimer's disease; amyloid peptide; metabolic syndrome.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / etiology*
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Brain / metabolism
  • Brain / pathology
  • Humans
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / metabolism
  • Insulin Resistance
  • Lipid Metabolism
  • Metabolic Syndrome / complications*
  • Neurons / metabolism
  • Neurons / pathology
  • Oxidative Stress
  • Protein Aggregation, Pathological
  • Proteolysis
  • Risk Factors
  • Signal Transduction

Substances

  • Amyloid beta-Peptides