A study on the features of memory impairment and neuropathology in crossbreed mice of Tg2576 and S100A9 knockout mice model

Abstract

Our previous study presented evidence that the inflammation-related S100A9 gene is significantly upregulated in the brains of Alzheimers Disease (AD) animal models and human AD patients. In addition, experiments have shown that knockdown of S100A9 expression improves cognition function in AD model mice (Tg2576), and these animals exhibit reduced amyloid plaque burden. In this study, I established a new transgenic animal model of AD by crossbreeding Tg2576 mouse with the S100A9 knockout (KO) mouse. I observed that S100A9 KO/Tg2576 (KO/Tg) mice displayed an increased spatial reference memory in Morris water maze and Y-maze tasks as well as decreased amyloid beta peptide (Aβ) neuropathology because of reduced levels of Aβ, C-terminal fragments of APP (APP-CT) and phosphorylated tau and increased expression of anti-inflammatory IL-10 and also decreased expression of inflammatory IL-6 and tumor neurosis factor (TNF)-α when compared with age-matched S100A9 WT/Tg2576 (WT/Tg) mice. Overall, these results suggest that S100A9 is responsible for the neurodegeneration and cognitive deficits in Tg2576 mice. The mechanism of S100A9 is able to coincide with the process of inflammatory cytokines. These findings indicate that knockout of S100A9 is a potential target for the pharmacological therapy of AD.