Prophylactic liraglutide treatment prevents amyloid plaque deposition, chronic inflammation and memory impairment in APP/PS1 mice

Behav Brain Res. 2015 Oct 15:293:96-106. doi: 10.1016/j.bbr.2015.07.024. Epub 2015 Jul 20.

Abstract

Type 2 diabetes is a risk factor for Alzheimer's disease (AD). Previously, we have shown that the diabetes drug liraglutide is protective in middle aged and in old APP/PS1 mice. Here, we show that liraglutide has prophylactic properties. When injecting liraglutide once-daily ip. in two months old mice for 8 months, the main hallmarks of AD were much reduced. Memory formation in object recognition and Morris water maze were normalised and synapse loss and the loss of synaptic plasticity was prevented. In addition, amyloid plaque load, including dense core congophilic plaques, was much reduced. Chronic inflammation (activated microglia) was also reduced in the cortex, and neurogenesis was enhanced in the dentate gyrus. The results demonstrate that liraglutide may protect from progressive neurodegeneration that develops in AD. The drug is currently in clinical trials in patients with AD.

Keywords: LTP; growth factor; incretin; insulin; memory loss; synaptic loss.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / complications
  • Alzheimer Disease / genetics
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Blood Glucose / drug effects
  • Blood Glucose / genetics
  • Body Weight / drug effects
  • Body Weight / genetics
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / genetics
  • Hippocampus / pathology
  • Hypoglycemic Agents / therapeutic use*
  • Inflammation / genetics
  • Inflammation / prevention & control*
  • Liraglutide / therapeutic use*
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / genetics
  • Maze Learning / drug effects
  • Memory Disorders / genetics
  • Memory Disorders / prevention & control*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Patch-Clamp Techniques
  • Plaque, Amyloid / drug therapy
  • Plaque, Amyloid / metabolism*
  • Presenilin-1 / genetics
  • Recognition, Psychology / drug effects

Substances

  • Amyloid beta-Protein Precursor
  • Blood Glucose
  • Hypoglycemic Agents
  • Presenilin-1
  • Liraglutide