Hippocampal Aβ expression, but not phosphorylated tau, predicts cognitive deficits following repeated peripheral poly I: C administration

J. D. White, M. J. Eimerbrink, H. B. Hayes, A. Hardy, E. A. Van Enkevort, J. L. Peterman, M. J. Chumley, G. W. Boehm

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Alzheimer's disease is marked by the accumulation of the amyloid-beta (Aβ) peptide, and increases in phosphorylation of the microtubule associated protein, tau. Changes in these proteins are considered responsible, in part, for the progressive neuronal degeneration and cognitive deficits seen in AD. We examined the effect of repeated consecutive peripheral poly I:C injections on cognitive deficits, central Aβ, and phosphorylated tau accumulation, following three treatment durations: 7, 14, and 21 days. Forty-eight hours after the final injection, animals were trained in a contextual fear-conditioning paradigm, and tested 24 h later. Immediately after testing, the hippocampus was collected to quantify Aβ and phosphorylated tau accumulation. Results showed that, although poly I:C-induced Aβ was significantly elevated at all time points examined, poly I:C only disrupted cognition after 14 and 21 days of administration. Moreover, elevations in phosphorylated tau were not seen until the 14-day time point. Interestingly, phosphorylated tau expression then declined at the 21-day time point. Finally, we demonstrated that Aβ levels are a stronger predictor of cognitive dysfunction, explaining 37% of the variance, whereas phosphorylated tau levels only accounted for 0.2%. Taken together, these results support the hypothesis that inflammation-induced elevation in Aβ disrupts cognition, independently of phosphorylated tau, and suggest that long-term administration of poly I:C may provide a model to investigate the contribution of long-term inflammation toward the development of Alzheimer's-like pathology.

Original languageEnglish (US)
Pages (from-to)219-225
Number of pages7
JournalBehavioural Brain Research
Volume313
DOIs
StatePublished - Oct 15 2016

Keywords

  • Alzheimer's disease
  • Amyloid-beta
  • Cognition
  • Inflammation
  • Mice
  • Tau

ASJC Scopus subject areas

  • Behavioral Neuroscience

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    White, J. D., Eimerbrink, M. J., Hayes, H. B., Hardy, A., Van Enkevort, E. A., Peterman, J. L., Chumley, M. J., & Boehm, G. W. (2016). Hippocampal Aβ expression, but not phosphorylated tau, predicts cognitive deficits following repeated peripheral poly I: C administration. Behavioural Brain Research, 313, 219-225. https://doi.org/10.1016/j.bbr.2016.07.032