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

McClean, Paula L. and Jalewa, Jaishree and Holscher, Christian (2015) Prophylactic liraglutide treatment prevents amyloid plaque deposition, chronic inflammation and memory impairment in APP/PS1 mice. Behavioural Brain Research, 293. pp. 96-106. ISSN 0166-4328

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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.

Item Type:
Journal Article
Journal or Publication Title:
Behavioural Brain Research
Additional Information:
This is the author’s version of a work that was accepted for publication in Behavioural Brain Research. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Behavioural Brain Research, 293, 2015 DOI: 10.1016/j.bbr.2015.07.024
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2800/2802
Subjects:
ID Code:
75650
Deposited By:
Deposited On:
03 May 2016 13:02
Refereed?:
Yes
Published?:
Published
Last Modified:
27 Oct 2020 05:07