Two different immunostaining patterns of beta-amyloid precursor protein (APP) may distinguish traumatic from nontraumatic axonal injury

Abstract

Immunostaining for beta-amyloid precursor protein (APP) is recognized as an effective tool for detecting traumatic axonal injury, but it also detects axonal injury due to ischemic or other metabolic causes. Previously, we reported two different patterns of APP staining: labeled axons oriented along with white matter bundles (pattern 1) and labeled axons scattered irregularly (pattern 2) (Hayashi et al. (Leg Med (Tokyo) 11:S171-173, 2009). In this study, we investigated whether these two patterns are consistent with patterns of trauma and hypoxic brain damage, respectively. Sections of the corpus callosum from 44 cases of blunt head injury and equivalent control tissue were immunostained for APP. APP was detected in injured axons such as axonal bulbs and varicose axons in 24 of the 44 cases of head injuries that also survived for three or more hours after injury. In 21 of the 24 APP-positive cases, pattern 1 alone was observed in 14 cases, pattern 2 alone was not observed in any cases, and both patterns 1 and 2 were detected in 7 cases. APP-labeled injured axons were detected in 3 of the 44 control cases, all of which were pattern 2. These results suggest that pattern 1 indicates traumatic axonal injury, while pattern 2 results from hypoxic insult. These patterns may be useful to differentiate between traumatic and nontraumatic axonal injuries.

Neurodegenerative pathways as targets for acquired epilepsy therapy development

“…Numerous lines of evidence in both humans and in pre‐clinical transgenic models that express APP have demonstrated that an epileptogenic brain injury triggers overexpression of APP . An increase in APP immunoreactivity has been shown in neurons and astrocytes in the weight drop model of TBI .…”

APP as a Protective Factor in Acute Neuronal Insults

“…A history of TBI prior to the onset of dementia correlates with greater amyloid burden in patients with mild cognitive deficits (Mielke et al, 2014 ) and is associated with faster rates of cognitive decline in AD patients (Moretti et al, 2012 ; Gilbert et al, 2014 ). In TBI patients, APP transcription is upregulated and its axonal transport is interrupted due to diffuse axonal injury, which results in deposition of APP and its products in axonal “bulbs” (Hayashi et al, 2015 ). These results from human studies are in line with a large body of evidence from various models of TBI in mice, rats and sheep, where APP overexpression following TBI has been extensively studied.…”

Transactive DNA Binding Protein 43 Rather Than Other Misfolded Proteins in the Brain is Associated with Islet Amyloid Polypeptide in Pancreas in Aged Subjects with Diabetes Mellitus

“…This finding was further highlighted by Ridler [40]. One factor that should be considered in the described experimental setting by Moreno-Gonzales and colleagues is the physiological increase of amyloid-β protein precursor (AβPP) production seen in posttraumatic brains [41]. Thus, the inoculation of pancreatic aggregates into the brain (a trauma) as was carried out by Moreno-Gonzales and colleagues might cause a physiological increase in AβPP production that in a setting of AβPP transgenic mice might lead to Aβ aggregation.…”