title: Hippocampal Aβ expression, but not phosphorylated tau, predicts cognitive deficits following repeated peripheral poly I:C administration.
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 24h 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.
authors.affiliation: Department of Psychology, Texas Christian University, United States.
authors.forename: J D
authors.initials: JD
authors.lastname: White
authors.affiliation: Department of Psychology, Texas Christian University, United States.
authors.forename: M J
authors.initials: MJ
authors.lastname: Eimerbrink
authors.affiliation: Department of Biology, Texas Christian University, United States.
authors.forename: H B
authors.initials: HB
authors.lastname: Hayes
authors.affiliation: Department of Biology, Texas Christian University, United States.
authors.forename: A
authors.initials: A
authors.lastname: Hardy
authors.affiliation: Department of Psychology, Texas Christian University, United States.
authors.forename: E A
authors.initials: EA
authors.lastname: Van Enkevort
authors.affiliation: Department of Psychology, Texas Christian University, United States.
authors.forename: J L
authors.initials: JL
authors.lastname: Peterman
authors.affiliation: Department of Biology, Texas Christian University, United States.
authors.forename: M J
authors.initials: MJ
authors.lastname: Chumley
authors.affiliation: Department of Psychology, Texas Christian University, United States. Electronic address: g.boehm@tcu.edu.
authors.forename: G W
authors.initials: GW
authors.lastname: Boehm
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000378:metabolism*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011066:Poly C / Q000008:administration & dosage / Q000494:pharmacology*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins; D011066:Poly C
keywords: Alzheimer’s disease; Amyloid-beta; Cognition; Inflammation; Mice; Tau