Accumulation of amyloid beta and tau and the formation of neurofilament inclusions following diffuse brain injury in the pig.
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.
Smith
D H
DH
Department of Neurosurgery, University of Pennsylvania, Philadelphia 19104, USA.
Chen
X H
XH
Nonaka
M
M
Trojanowski
J Q
JQ
Lee
V M
VM
Saatman
K E
KE
Leoni
M J
MJ
Xu
B N
BN
Wolf
J A
JA
Meaney
D F
DF
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology* / Q000523:psychology; D005260:Female; D002479:Inclusion Bodies / Q000378:metabolism* / Q000473:pathology; D008297:Male; D016900:Neurofilament Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D013552:Swine; D013556:Swine, Miniature; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D016900:Neurofilament Proteins; D016875:tau Proteins