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

Paula L McClean, Jaishree Jalewa, Christian Hölscher

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42 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)96-106
Number of pages11
JournalBehavioural Brain Research
Volume293
Early online date20 Jul 2015
DOIs
Publication statusPublished - 15 Oct 2015

Keywords

  • memory loss
  • synaptic loss
  • growth factor
  • insulin
  • incretin
  • LTP

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