βCTF-Correlated Burst of Hippocampal TNFα Occurs at a Very Early, Pre-Plaque Stage in the TgCRND8 Mouse Model of Alzheimer's Disease

Tumor necrosis factor-alpha (TNF alpha) regulates neuronal excitability. We investigated whether alterations in the level of TNF alpha 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 TNF alpha expression in 1-month-old TgCRND8 mice that correlated with levels of the beta-C-terminal fragment (beta CTF) of amyloid-beta 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 TNF alpha increase during this pre-symptomatic stage of AD-like pathology.