A Lack of Amyloid β Plaques Despite Persistent Accumulation of Amyloid β in Axons of Long-Term Survivors of Traumatic Brain Injury

Authors

  • Xiao-Han Chen,

    1. Department of Neurosurgery, School of Medicine, University of Pennsylvania,
    2. Penn Center for Brain Injury and Repair,
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  • Victoria E. Johnson,

    1. Department of Neurosurgery, School of Medicine, University of Pennsylvania,
    2. Penn Center for Brain Injury and Repair,
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  • Kunihiro Uryu,

    1. The Center for Neurodegenerative Disease Research, Pathology and Laboratory Medicine, and
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  • John Q. Trojanowski,

    1. Department of Neurosurgery, School of Medicine, University of Pennsylvania,
    2. Penn Center for Brain Injury and Repair,
    3. The Center for Neurodegenerative Disease Research, Pathology and Laboratory Medicine, and
    4. Institute of Aging. University of Pennsylvania, Philadelphia, Pa.
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  • Douglas H. Smith

    Corresponding author
    1. Department of Neurosurgery, School of Medicine, University of Pennsylvania,
    2. Penn Center for Brain Injury and Repair,
      Douglas H. Smith, MD, Department of Neurosurgery, University of Pennsylvania, 105 Hayden Hall, 3320 Smith Walk, Philadelphia, PA 19104-6316 (E-mail: smithdou@mail.med.upenn.edu)
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Douglas H. Smith, MD, Department of Neurosurgery, University of Pennsylvania, 105 Hayden Hall, 3320 Smith Walk, Philadelphia, PA 19104-6316 (E-mail: smithdou@mail.med.upenn.edu)

Abstract

Traumatic brain injury (TBI) is a risk factor for developing Alzheimer's disease (AD). Additionally, TBI induces AD-like amyloid β (Aβ) plaque pathology within days of injury potentially resulting from massive accumulation of amyloid precursor protein (APP) in damaged axons. Here, progression of Aβ accumulation was examined using brain tissue from 23 cases with post-TBI survival of up to 3 years. Even years after injury, widespread axonal pathology was consistently observed and was accompanied by intra-axonal co-accumulations of APP with its cleavage enzymes, beta-site APP cleaving enzyme and presenilin-1 and their product, Aβ. However, in marked contrast to the plaque pathology noted in short-term cases post TBI, virtually no Aβ plaques were found in long-term survivors. A potential mechanism for Aβ plaque regression was suggested by the post-injury accumulation of an Aβ degrading enzyme, neprilysin. These findings fail to support the premise that progressive plaque pathology after TBI ultimately results in AD.

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