The incretin hormones glucagonlike peptide 1 and glucose-dependent insulinotropic polypeptide are neuroprotective in mouse models of Alzheimer's disease

Hölscher, Christian (2014) The incretin hormones glucagonlike peptide 1 and glucose-dependent insulinotropic polypeptide are neuroprotective in mouse models of Alzheimer's disease. Alzheimer's and Dementia, 10 (1 Supp). S47-54. ISSN 1552-5260

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Abstract

The incretin hormones glucagonlike peptide 1 and glucose-dependent insulinotropic polypeptide (GIP) have been developed to treat type 2 diabetes and also act as growth factors. We have tested several long-acting incretin mimetics in the amyloid precursor protein (APP)(Swe)/presenilin 1 (PS1)(ΔE9) model of Alzheimer's disease (AD). We found that liraglutide, lixisenatide, and D-Ala2-GIP cross the blood-brain barrier and prevent the impairment in memory formation and synaptic plasticity, increase synapse numbers, reduce amyloid plaque load and soluble amyloid-β levels, reduce oxidative stress and the chronic inflammation response in the brain, enhance the proliferation of neuronal progenitor cells, and increase neurogenesis in the dentate gyrus. In an (18)fluorodeoxyglucoe positron emission tomographic/computed tomographic imaging study in PLB1-triple mice, a mouse model that expresses human mutated APP, PS1, and tau proteins, glucose metabolism was found to be normalized in forebrain areas after liraglutide treatment, demonstrating that neuronal metabolic activity was normalized. A clinical trial testing liraglutide in patients with AD is currently ongoing.

Item Type:
Journal Article
Journal or Publication Title:
Alzheimer's and Dementia
Additional Information:
Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2800/2806
Subjects:
ID Code:
69047
Deposited By:
Deposited On:
02 Apr 2014 08:41
Refereed?:
Yes
Published?:
Published
Last Modified:
17 Jun 2020 02:46