Journal Article

Subacute Changes in Cleavage Processing of Amyloid Precursor Protein and Tau following Penetrating Traumatic Brain Injury

Hwang, Hye, Mountney, Andrea, Tortella, Frank C., Shear, Deborah A., Schmid, Kara E., Cartagena, Casandra M., Rammelkamp, Zoe, Boutte, Angela M., Swiercz, Adam

2016

Overview

Traumatic brain injury (TBI) is an established risk factor for the development of Alzheimer's disease (AD). Here the effects of severe penetrating TBI on APP and tau cleavage processing were investigated in a rodent model of penetrating ballistic-like brain injury (PBBI). PBBI was induced by stereotactically inserting a perforated steel probe through the right frontal cortex of the anesthetized rat and rapidly inflating/deflating the probe's elastic tubing into an elliptical shaped balloon to 10% of total rat brain volume causing temporary cavitation injury. Separate animals underwent probe injury (PrI) alone without balloon inflation. Shams underwent craniectomy. Brain tissue was collected acutely (4h, 24h, 3d) and subacutely (7d) post-injury and analyzed by immunoblot for full length APP (APP-FL) and APP beta c-terminal fragments (βCTFs), full length tau (tau-FL) and tau truncation fragments and at 7d for cytotoxic Beta amyloid (Aβ) peptides Aβ40 and Aβ42 analysis. APP-FL was significantly decreased at 3d and 7d following PBBI whereas APP βCTFs were significantly elevated by 4h post-injury and remained elevated through 7d post-injury. Effects on βCTFs were mirrored with PrI, albeit to a lesser extent. Aβ40 and Aβ42 were significantly elevated at 7d following PBBI and PrI. Tau-FL decreased substantially 3d and 7d post-PBBI and PrI. Importantly, a 22 kDa tau fragment (tau22), similar to that found in AD, was significantly elevated by 4h and remained elevated through 7d post-injury. Thus both APP and tau cleavage was dramatically altered in the acute and subacute periods post-injury. As cleavage of these proteins has also been implicated in AD, TBI pathology shown here may set the stage for the later development of AD or other tauopathies.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Alzheimer's disease / Amyloid beta-protein / Amyloid beta-Protein Precursor - analysis / Amyloid beta-Protein Precursor - metabolism / Amyloid precursor protein / Analysis / Animals / Ballistic penetration / Biology and Life Sciences / Brain / Brain - metabolism / Brain - pathology / Brain injuries / Brain Injuries, Traumatic - metabolism / Brain Injuries, Traumatic - pathology / Brain research / Casualties / Cavitation / Cleavage / Cortex (frontal) / Cytotoxicity / Fragmentation / Fragments / Head injuries / Head Injuries, Penetrating - metabolism / Head Injuries, Penetrating - pathology / Health aspects / Health risks / Inflating / Influence / Injury analysis / Male / Medicine and Health Sciences / Mutation / Neurodegenerative diseases / Neurosciences / Pathology / Peptides / Phosphorylation / Physical Sciences / Precursors / Proteins / Psychiatry / Rats, Sprague-Dawley / Research and Analysis Methods / Risk factors / Steel / Studies / Tau protein / tau Proteins - analysis / tau Proteins - metabolism / Tortella / Trauma / Traumatic brain injury / β-Amyloid