| First Author | Faivre E | Year | 2013 |
| Journal | J Alzheimers Dis | Volume | 35 |
| Issue | 2 | Pages | 267-83 |
| PubMed ID | 23568101 | Mgi Jnum | J:269949 |
| Mgi Id | MGI:6275872 | Doi | 10.3233/JAD-121888 |
| Citation | Faivre E, et al. (2013) D-Ala2GIP facilitated synaptic plasticity and reduces plaque load in aged wild type mice and in an Alzheimer's disease mouse model. J Alzheimers Dis 35(2):267-83 |
| abstractText | Type 2 diabetes mellitus has been identified as a risk factor for Alzheimer's disease (AD). We have previously shown that glucose-dependent insulinotropic polypeptide (GIP) analogues that originally have been developed to treat diabetes have neuroprotective effects in the brains of the APPswe/PS1DeltaE9 mouse model of AD. In a previous study, the analogue D-Ala2GIP intraperitoneally (i.p.) in 12 months old animals, an age that represents early phase AD, D-Ala2GIP improved memory in wild type (WT) mice and rescued the cognitive decline of 12 months old AbetaPP/PS1 mice. Synapse numbers and synaptic plasticity was also protected. Importantly, the amyloid plaque load in the cortex was reduced. In the present study, we tested D-Ala2GIP in 19 months old AbetaPP/PS1 mice or littermate controls to find out if the drug may have protective effects even at an advanced stage of AD. Mice were injected for 21 days at 25 nmol/kg i.p. once daily. Interestingly, the age-related reduction of synaptic numbers in the DG and cortex was prevented in WT control mice. D-Ala2GIP facilitated synaptic plasticity in AbetaPP/PS1 and WT mice and reduced the number of amyloid plaques and activated microglia in the cortex of AbetaPP/PS1 mice. The results show that D-Ala2GIP not only has protective but also regenerative properties in the brain of aged WT mice, and on key biomarkers found in AD in AbetaPP/PS1 mice. This suggests that novel GIP analogues may have beneficial effects in non-demented aged people and perhaps even in AD patients even when the disease is further progressed. |
