Streptozotocin-induced diabetes increases amyloid plaque deposition in AD transgenic mice through modulating AGEs/RAGE/NF-κB pathway

An increasing number of studies have demonstrated of that diabetes mellitus (DM) is associated with an increased prevalence of Alzheimer disease (AD), the underlying mechanisms are still obscure.We developed a streptozotocin (STZ)-induced diabetic AD transgenic mouse model and evaluated the effect of hyperglycemia on senile plaque formation.Our data showed that administration of STZ increased the level of blood glucose and increased the advanced glycation end products (AGEs) in brain tissue, and further enhanced the expression levels of the receptor for AGEs (RAGE) and the nuclear factor-kappa B (NF-κB) in the brain, and accelerated the senile plaque formation in the transgenic mice. Our results showed that STZ-induced insulin-deficient hyperglycemia caused the pathophysiology of AD in APP/PS1 transgenic mice by modulating the AGEs/RAGE/NF-κB pathway.Our study suggests that there is a close linkage of DM and cerebral amyloidosis in the pathogenesis of AD.