BACE1 RNA interference improves spatial memory and attenuates Aβ burden in a streptozotocin-induced tau hyperphosphorylated rat model.

Both senile plaques and intracellular neurofibrillary tangles are important pathological characteristics in Alzheimer's disease. However, the relationship between Aβ deposition and tau hyperphosphorylation is unknown. In this study, the increased levels of full-length amyloid precursor protein (APP), APP C-terminal fragment (β-CTF) and BACE1 were found in streptozotocin-induced tau hyperphosphorylation models by quantitative polymerase chain reaction, Western blotting and immunohistochemistry methods. In the previous studies, few strategies focusing on inhibiting β-secretase (BACE1) in a tau hyperphosphorylation model were utilized. Here, BACE1 RNAi was used to treat the streptozotocin-induced tau hyperphosphorylation animal models. BACE1 RNAi treatment improved the behavioural ability of animal models and reduced the amount of Aβ1-40 and Aβ1-42, accompanied by decreasing the levels of BACE1 and β-CTF. Our results demonstrated that neurological defects and neurotoxic fragments, including Aβ and β-CTF, were eliminated by BACE1 RNAi in the tau hyperphosphorylated model, implying the efficiency and safety of BACE1RNAi treatment against Alzheimer's disease.