Vildagliptin: an anti-diabetes agent ameliorates cognitive deficits and pathology observed in streptozotocin-induced Alzheimer's disease

ObjectivesAdults who develop type 2 diabetes (T2D) at later stages are at a higher risk of developing Alzheimer's disease (AD). Pharmacological agents such as dipeptidyl peptidase-4 (DPP-4) inhibitors that increase the levels of glucagon-like peptide-1 (GLP-1) and ameliorate T2D have also become promising candidates as disease-modifying agents in the treatment of AD. The present study investigates the efficacy of vildagliptin, a DPP-4 inhibitor in a streptozotocin (STZ)-induced rat model of AD. MethodsThree months following the induction of AD by intracerebral injection of STZ, animals were orally administered with vildagliptin (2.5, 5 and 10mg/kg) for 30 days. Dose-dependent and time-course effects of vildagliptin on memory retention were investigated during the course of treatment. Following treatment, the animals were sacrificed, and brain tissues were used to evaluate the effects of vildagliptin on hippocampal and cortical GLP-1 levels, amyloid beta (A) burden, tau phosphorylation and inflammatory markers. Key findingsThe results reveal a time-dependent improvement in memory retention and a dose-dependent attenuation of A, tau phosphorylation and inflammatory markers and increased GLP-1 levels. ConclusionsThese robust therapeutic effects of vildagliptin demonstrate a unique mechanism for A and tau clearance and reverse the cognitive deficits and pathology observed in AD.