Insulin resistance, dyslipidemia, and apolipoprotein E interactions as mechanisms in cognitive impairment and Alzheimer's disease

Exp Biol Med (Maywood). 2016 Sep;241(15):1676-83. doi: 10.1177/1535370216660770. Epub 2016 Jul 28.


An increased risk for Alzheimer's disease is associated with dyslipidemia and insulin resistance. A separate literature shows the genetic risk for developing Alzheimer's disease is strongly correlated to the presence of the E4 isoform of the apolipoprotein E carrier protein. Understanding how apolipoprotein E carrier protein, lipids, amyloid β peptides, glucose, central nervous system insulin, and peripheral insulin interact with one another in Alzheimer's disease is an area of increasing interest. Here, we will review the evidence relating apolipoprotein E carrier protein, lipids, and insulin action to Alzheimer's disease and Aβ peptides and then propose mechanisms as to how these factors might interact with one another to impair cognition and promote Alzheimer's disease.

Keywords: Alzheimer's disease; apolipoprotein E; cognition; dyslipidemia; insulin resistance.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / etiology*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Peptides / physiology
  • Apolipoproteins E / metabolism
  • Apolipoproteins E / physiology*
  • Cognitive Dysfunction / etiology*
  • Cognitive Dysfunction / metabolism
  • Cognitive Dysfunction / physiopathology
  • Dyslipidemias / complications*
  • Dyslipidemias / physiopathology
  • Humans
  • Insulin Resistance / physiology*


  • Amyloid beta-Peptides
  • Apolipoproteins E