Insulin signalling in Alzheimer's disease and diabetes: from epidemiology to molecular links

J Intern Med. 2016 Nov;280(5):430-442. doi: 10.1111/joim.12534. Epub 2016 Oct 14.

Abstract

As populations across the world both age and become more obese, the numbers of individuals with Alzheimer's disease and diabetes are increasing; posing enormous challenges for society and consequently becoming priorities for governments and global organizations. These issues, an ageing population at risk of neurodegenerative diseases such as Alzheimer's disease and an increasingly obese population at risk of metabolic alterations such as type 2 diabetes, are usually considered as independent conditions, but increasing evidence from both epidemiological and molecular studies link these disorders. The aim of this review was to highlight these multifactorial links. We will discuss the impact of direct links between insulin and IGF-1 signalling and the Alzheimer's disease-associated pathological events as well as the impact of other processes such as inflammation, oxidative stress and mitochondrial dysfunction either common to both conditions or perhaps responsible for a mechanistic link between metabolic and neurodegenerative disease. An understanding of such associations might be of importance not only in the understanding of disease mechanisms but also in the search for novel therapeutic options.

Keywords: Alzheimer's disease; beta-amyloid; diabetes; inflammation; insulin; tau.

Publication types

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

MeSH terms

  • Aging / metabolism
  • Alzheimer Disease / complications
  • Alzheimer Disease / metabolism*
  • Animals
  • Brain / metabolism
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / metabolism*
  • Humans
  • Inflammation / metabolism
  • Insulin / metabolism*
  • Insulin-Like Growth Factor I / metabolism*
  • Mitochondria / metabolism
  • Neurons / metabolism
  • Oxidative Stress
  • Signal Transduction

Substances

  • Insulin
  • Insulin-Like Growth Factor I