Neuroprotective effects of D-Ala2GIP on Alzheimer’s disease biomarkers in an APP/PS1 mouse model

Faivre, Emilie and Holscher, Christian (2013) Neuroprotective effects of D-Ala2GIP on Alzheimer’s disease biomarkers in an APP/PS1 mouse model. Alzheimer's Research and Therapy, 5. pp. 20-29.

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Abstract

Type 2 diabetes mellitus has been identified as a risk factor for Alzheimer's disease (AD). An impairment of insulin signaling as well as a desensitization of its receptor has been found in AD brains. Glucose-dependent insulinotropic polypeptide (GIP) normalises insulin signaling by facilitating insulin release. GIP directly modulates neurotransmitter release, LTP formation, and protects synapses from the detrimental effects of beta-amyloid fragments on LTP formation, and cell proliferation of progenitor cells in the dentate gyrus. Here we investigate the potential therapeutic property of the new long lasting incretin hormone analogue D-Ala2GIP on key symptoms found in a mouse model of Alzheimer' disease (APPswe/PS1detaE9). METHODS: D-Ala2GIP was injected for 21 days at 25 nmol/kg ip once daily in APP/PS1 male mice and wild type (WT) littermates aged 6 or 12 months of age. Amyloid plaque load, inflammation biomarkers, synaptic plasticity in the brain (LTP), and memory were measured. RESULTS: D-Ala2GIP improved memory in WT mice and rescued the cognitive decline of 12 months old APP/PS1 mice in two different memory tasks. Furthermore, deterioration of synaptic function in the dentate gyrus and cortex was prevented in 12 months old APP/PS1 mice. D-Ala2GIP facilitated synaptic plasticity in APP/PS1 and WT mice and reduced the number of amyloid plaques in the cortex of D-Ala2GIP injected APP/PS1 mice. The inflammatory response in microglia was also reduced. CONCLUSION: The results demonstrate that D-Ala2GIP has neuroprotective properties on key hallmarks found in AD. This finding shows that novel GIP analogues have the potential as a novel therapeutic for AD.

Item Type:
Journal Article
Journal or Publication Title:
Alzheimer's Research and Therapy
Additional Information:
© 2013 Faivre et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2800/2808
Subjects:
ID Code:
67567
Deposited By:
Deposited On:
18 Nov 2013 09:58
Refereed?:
Yes
Published?:
Published
Last Modified:
12 Jul 2020 04:27