title: Prophylactic liraglutide treatment prevents amyloid plaque deposition, chronic inflammation and memory impairment in APP/PS1 mice.
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.
authors.affiliation: Clinical, Translational and Research Innovation Centre (C-TRIC), Ulster University, Derry/Londonderry, BT47 6SB, Northern Ireland, UK.
authors.forename: Paula L
authors.initials: PL
authors.lastname: McClean
authors.affiliation: Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, LA1 4YQ, UK.
authors.forename: Jaishree
authors.initials: J
authors.lastname: Jalewa
authors.affiliation: Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, LA1 4YQ, UK. Electronic address: c.holscher@lancaster.ac.uk.
authors.forename: Christian
authors.initials: C
authors.lastname: Hölscher
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000235:genetics; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D006624:Hippocampus / Q000473:pathology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007249:Inflammation / Q000235:genetics / Q000517:prevention & control*; D000069450:Liraglutide / Q000627:therapeutic use*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000235:genetics / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018408:Patch-Clamp Techniques; D058225:Plaque, Amyloid / Q000188:drug therapy / Q000378:metabolism*; D053764:Presenilin-1 / Q000235:genetics; D021641:Recognition, Psychology / Q000187:drug effects
chemical_list: D016564:Amyloid beta-Protein Precursor; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D053764:Presenilin-1; D000069450:Liraglutide
keywords: LTP; growth factor; incretin; insulin; memory loss; synaptic loss