| First Author | D'Amico M | Year | 2010 |
| Journal | Exp Gerontol | Volume | 45 |
| Issue | 3 | Pages | 202-7 |
| PubMed ID | 20005285 | Mgi Jnum | J:158446 |
| Mgi Id | MGI:4438811 | Doi | 10.1016/j.exger.2009.12.004 |
| Citation | D'Amico M, et al. (2010) Long-term inhibition of dipeptidyl peptidase-4 in Alzheimer's prone mice. Exp Gerontol 45(3):202-7 |
| abstractText | We tested here the impact of a long-term inhibition of dipeptidyl peptidase-4 (DPP-4) with sitagliptin on the deposition of amyloid-beta within the brain and deficits in memory-related behavioral paradigms in a model of Alzheimer's disease (AD): double transgenic mice B6*Cg-Tg(APPswe,PSEN1dE9)85Dbo/J. Mice began to receive sitagliptin at 7 months of age. Three different dose of sitagliptin (5, 10 and 20 mg/kg), were administered daily for 12 weeks by gastric gavage. The treatments counteracted: (i) the memory impairment in the contextual fear conditioning test; (ii) increased the brain levels of GLP-1; (iii) produced significant reductions of nitrosative stress and inflammation hallmarks within the brain, as well as (iv) a significant diminution in the ultimate number and total area of betaAPP and Abeta deposits. All these effects much more evident for the dose of 20 mg/kg sitagliptin. The long-term inhibition of the endogenous DPP-4 enzymes with sitagliptin can significantly delay some forms of AD pathology, including amyloid deposition, when administered early in the disease course of a transgenic mouse model of AD. |
