βCTF-correlated burst of hippocampal TNFα occurs at a very early, pre-plaque stage in the TgCRND8 mouse model of Alzheimer's disease

Abstract

Tumor necrosis factor-alpha (TNFα) regulates neuronal excitability. We investigated whether alterations in the level of TNFα occur at a time point that precedes the reported seizure-associated hyperexcitability of hippocampal networks in pre-plaque models of Alzheimer's disease (AD). Western blot and ELISA experiments indicated a significant increase in hippocampal TNFα expression in 1-month-old TgCRND8 mice that correlated with levels of the β-C-terminal fragment (βCTF) of amyloid-β protein precursor. CD11b labeling indicated changes in microglial morphology toward an activated state, suggesting that these cells may be a putative source of the observed TNFα increase during this pre-symptomatic stage of AD-like pathology.