Amyloid β accumulation in axons after traumatic brain injury in humans

Douglas H. Smith Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania; and Department of Neuropathology, Institute of Neurological Sciences, Southern General Hospital, Glasgow, Scotland

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Xiao-han Chen Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania; and Department of Neuropathology, Institute of Neurological Sciences, Southern General Hospital, Glasgow, Scotland

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Akira Iwata Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania; and Department of Neuropathology, Institute of Neurological Sciences, Southern General Hospital, Glasgow, Scotland

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David I. Graham Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania; and Department of Neuropathology, Institute of Neurological Sciences, Southern General Hospital, Glasgow, Scotland

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Object. Although plaques composed of amyloid β (Aβ) have been found shortly after traumatic brain injury (TBI) in humans, the source for this Aβ has not been identified. In the present study, the authors explored the potential relationship between Aβ accumulation in damaged axons and associated Aβ plaque formation.

Methods. The authors performed an immunohistochemical analysis of paraffin-embedded sections of brain from 12 patients who died after TBI and from two control patients by using antibodies selective for Aβ peptides, amyloid precursor protein (APP), and neurofilament (NF) proteins. In nine brain-injured patients, extensive colocalizations of Aβ, APP, and NF protein were found in swollen axons. Many of these immunoreactive axonal profiles were present close to Aβ plaques or were surrounded by Aβ staining, which spread out into the tissue. Immunoreactive profiles were not found in the brains of the control patients.

Conclusions. The results of this study indicate that damaged axons can serve as a large reservoir of Aβ, which may contribute to Aβ plaque formation after TBI in humans.

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