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: 20. pp. 20-29.

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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
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© 2013 Faivre et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Uncontrolled Keywords:
?? cognitive neuroscienceclinical neurologyneurology ??
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18 Nov 2013 09:58
Last Modified:
18 Jan 2024 00:14