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Cited by 260Alzheimer's disease research and treatmentsTraumatic Brain Injury and Neurovascular DisturbancesTraumatic Brain Injury Research

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Accumulation of Amyloid β and Tau and the Formation of Neurofilament Inclusions Following Diffuse Brain Injury in the Pig

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Smith, D. H., Chen, X-H, Nonaka, M., Trojanowski, J. Q., Lee, VM-Y, Saatman, K. E., Leoni, M. J., Xu, B-N, Wolf, J. A., Meaney, D. F.·1999·Journal of Neuropathology & Experimental Neurology
DOI 10.1097/00005072-199909000-00008PMC PMC13479983
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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 beta (A beta). 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 degrees 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 A beta, beta-amyloid precursor protein (betaPP), tau, and neurofilament (NF) proteins. In addition to diffuse axonal pathology, we detected accumulation of A beta and tau that colocalized with immunoreactive betaPP and NF in damaged axons throughout the white matter in all injured animals at 3-10 days post-trauma. In a subset of brain injured animals, diffuse A beta-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.

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Metadata

Authors
Smith, D. H., Chen, X.-H., Nonaka, M., Trojanowski, J. Q., Lee, V.-Y., Saatman, K. E., Leoni, M. J., Xu, B.-N., Wolf, J. A., & Meaney, D. F.
Affiliations
University of Pennsylvania (US)
Corresponding author
Smith, D. H.
ORCID
Venue
Journal of Neuropathology & Experimental Neurology
Publisher
Oxford University Press (OUP)
Published
1999-09
Volume
58
Issue
9
Pages
982-992
ISSN
  • 0022-3069 (ISSN-L)
  • 1554-6578
DOI
10.1097/00005072-199909000-00008
PMC
PMC13479983
OpenAlex
W2091184929
Cited by
260
References
0
Citations by year
2026: 2 · 2025: 5 · 2024: 5 · 2023: 7 · 2022: 10 · 2021: 8 · 2020: 9 · 2019: 17 · 2018: 12 · 2017: 13 · 2016: 15 · 2015: 14 · 2014: 11 · 2013: 15 · 2012: 14
FWCI
4.35
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuropathology & Experimental Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
Funders
  • National Institute on Aging (AG12527, R01AG012527, P30AG010124, P01AG009215)
  • National Institute of Neurological Disorders and Stroke (P50NS008803, R01NS038104, NS-08803, NS38104)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
Keywords
diffuse brain injury, traumatic brain injury, amyloid-beta, tau protein, neurofilaments, Alzheimer's disease, diffuse axonal injury, white matter, porcine model, amyloid precursor protein, neurodegeneration
MeSH terms
Animals, Axons, Behavior, Animal, Brain, Brain Injuries, Inclusion Bodies, Female, Male, Neurons, Swine, Swine, Miniature, Amyloid beta-Peptides, tau Proteins, Neurofilament Proteins

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