Accumulation of amyloid β and tau and the formation of neurofilament inclusions following diffuse brain injury in the pig

Douglas H. Smith, X. H. Chen, M. Nonaka, J. Q. Trojanowski, V. M.Y. Lee, K. E. Saatman, M. J. Leoni, B. N. Xu, J. A. Wolf, D. F. Meaney

Research output: Contribution to journalArticlepeer-review

211 Scopus citations

Abstract

Brain trauma in humans increases the risk for developing Alzheimer disease (AD) and may induce the acute formation of AD-like plaques containing amyloid β (Aβ). To further explore the potential link between brain trauma and neurodegeneration, we conducted neuropathological studies using a pig model of diffuse brain injury. Brain injury was induced in anesthetized animals via nonimpact head rotational acceleration of 110°over 20 ms in the coronal plane (n = 15 injured n = 3 noninjured). At 1, 3, 7, and 10 days post-trauma, control and injured animals were euthanized and immunohistochemical analysis was performed on brain sections using antibodies specific for Aβ, β-amyloid precursor protein (βPP), tau, and neurofilament (NF) proteins. In addition to diffuse axonal pathology, we detected accumulation of Aβ and tau that colocalized with immunoreactive βPP and NF in damaged axons throughout the white matter in all injured animals at 3-10 days posttrauma. In a subset of brain injured animals, diffuse Aβ-containing plaque-like profiles were found in both the gray and white matter, and accumulations of tau and NF rich inclusions were observed in neuronal perikarya. These results show that this pig model of diffuse brain injury is characterized by accumulations of proteins that also form pathological aggregates in AD and related neurodegenerative diseases.

Original languageEnglish
Pages (from-to)982-992
Number of pages11
JournalJournal of Neuropathology and Experimental Neurology
Volume58
Issue number9
DOIs
StatePublished - Sep 1999

Keywords

  • Alzheimer disease
  • Amyloid precursor protein
  • Amyloid β
  • Brain trauma
  • Neurodegeneration
  • Neurofilament Tau

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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