Detection of β-amyloid oligomers as a predictor of neurological outcome after brain injury: Laboratory investigation

Joshua Wayne Gatson, Victoria Warren, Kareem Abdelfattah, Steven Wolf, Linda S. Hynan, Carol Moore, Ramon Diaz-Arrastia, Joseph P. Minei, Christopher Madden, Jane G. Wigginton

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Object. Traumatic brain injury (TBI) is known to be a risk factor for Alzheimer-like dementia. In previous studies, an increase in β-amyloid (A) monomers, such as β-amyloid 42 (Aβ42), in the CSF of patients with TBI has been shown to correlate with a decrease in amyloid plaques in the brain and improved neurological outcomes. In this study, the authors hypothesized that the levels of toxic high-molecular-weight β-amyloid oligomers are increased in the brain and are detectable within the CSF of TBI patients with poor neurological outcomes. Methods. Samples of CSF were collected from 18 patients with severe TBI (Glasgow Coma Scale Scores 3-8) and a ventriculostomy. In all cases the CSF was collected within 72 hours of injury. The CSF levels of neuron-specific enolase (NSE) and Aβ42 were measured using enzyme-linked immunosorbent assay. The levels of high-molecularweight β-amyloid oligomers were measured using Western blot analysis. Results. Patients with good outcomes showed an increase in the levels of CSF Aβ42 (p = 0.003). Those with bad outcomes exhibited an increase in CSF levels of β-amyloid oligomers (p = 0.009) and NSE (p = 0.001). In addition, the CSF oligomer levels correlated with the scores on the extended Glasgow Outcome Scale (r = -0.89, p = 0.0001), disability rating scale scores (r = 0.77, p = 0.005), CSF Aβ42 levels (r = -0.42, p = 0.12), and CSF NSE levels (r = 0.70, p = 0.004). Additionally, the receiver operating characteristic curve yielded an area under the curve for β-amyloid oligomers of 0.8750 ± 0.09. Conclusions. Detection of β-amyloid oligomers may someday become a useful clinical tool for determining injury severity and neurological outcomes in patients with TBI.

Original languageEnglish (US)
Pages (from-to)1336-1342
Number of pages7
JournalJournal of Neurosurgery
Volume118
Issue number6
DOIs
StatePublished - Jun 2013

Fingerprint

Amyloid
Brain Injuries
Phosphopyruvate Hydratase
Ventriculostomy
Glasgow Outcome Scale
Glasgow Coma Scale
Poisons
Amyloid Plaques
Wounds and Injuries
Brain
ROC Curve
Area Under Curve
Alzheimer Disease
Molecular Weight
Western Blotting
Enzyme-Linked Immunosorbent Assay
Traumatic Brain Injury

Keywords

  • Amyloid oligomers
  • Amyloid-β42
  • Biomarkers
  • Cerebrospinal fluid
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

@article{b7d31138220141828a8318dff9eb62d9,
title = "Detection of β-amyloid oligomers as a predictor of neurological outcome after brain injury: Laboratory investigation",
abstract = "Object. Traumatic brain injury (TBI) is known to be a risk factor for Alzheimer-like dementia. In previous studies, an increase in β-amyloid (A) monomers, such as β-amyloid 42 (Aβ42), in the CSF of patients with TBI has been shown to correlate with a decrease in amyloid plaques in the brain and improved neurological outcomes. In this study, the authors hypothesized that the levels of toxic high-molecular-weight β-amyloid oligomers are increased in the brain and are detectable within the CSF of TBI patients with poor neurological outcomes. Methods. Samples of CSF were collected from 18 patients with severe TBI (Glasgow Coma Scale Scores 3-8) and a ventriculostomy. In all cases the CSF was collected within 72 hours of injury. The CSF levels of neuron-specific enolase (NSE) and Aβ42 were measured using enzyme-linked immunosorbent assay. The levels of high-molecularweight β-amyloid oligomers were measured using Western blot analysis. Results. Patients with good outcomes showed an increase in the levels of CSF Aβ42 (p = 0.003). Those with bad outcomes exhibited an increase in CSF levels of β-amyloid oligomers (p = 0.009) and NSE (p = 0.001). In addition, the CSF oligomer levels correlated with the scores on the extended Glasgow Outcome Scale (r = -0.89, p = 0.0001), disability rating scale scores (r = 0.77, p = 0.005), CSF Aβ42 levels (r = -0.42, p = 0.12), and CSF NSE levels (r = 0.70, p = 0.004). Additionally, the receiver operating characteristic curve yielded an area under the curve for β-amyloid oligomers of 0.8750 ± 0.09. Conclusions. Detection of β-amyloid oligomers may someday become a useful clinical tool for determining injury severity and neurological outcomes in patients with TBI.",
keywords = "Amyloid oligomers, Amyloid-β42, Biomarkers, Cerebrospinal fluid, Traumatic brain injury",
author = "Gatson, {Joshua Wayne} and Victoria Warren and Kareem Abdelfattah and Steven Wolf and Hynan, {Linda S.} and Carol Moore and Ramon Diaz-Arrastia and Minei, {Joseph P.} and Christopher Madden and Wigginton, {Jane G.}",
year = "2013",
month = "6",
doi = "10.3171/2013.2.JNS121771",
language = "English (US)",
volume = "118",
pages = "1336--1342",
journal = "Journal of Neurosurgery",
issn = "0022-3085",
publisher = "American Association of Neurological Surgeons",
number = "6",

}

TY - JOUR

T1 - Detection of β-amyloid oligomers as a predictor of neurological outcome after brain injury

T2 - Laboratory investigation

AU - Gatson, Joshua Wayne

AU - Warren, Victoria

AU - Abdelfattah, Kareem

AU - Wolf, Steven

AU - Hynan, Linda S.

AU - Moore, Carol

AU - Diaz-Arrastia, Ramon

AU - Minei, Joseph P.

AU - Madden, Christopher

AU - Wigginton, Jane G.

PY - 2013/6

Y1 - 2013/6

N2 - Object. Traumatic brain injury (TBI) is known to be a risk factor for Alzheimer-like dementia. In previous studies, an increase in β-amyloid (A) monomers, such as β-amyloid 42 (Aβ42), in the CSF of patients with TBI has been shown to correlate with a decrease in amyloid plaques in the brain and improved neurological outcomes. In this study, the authors hypothesized that the levels of toxic high-molecular-weight β-amyloid oligomers are increased in the brain and are detectable within the CSF of TBI patients with poor neurological outcomes. Methods. Samples of CSF were collected from 18 patients with severe TBI (Glasgow Coma Scale Scores 3-8) and a ventriculostomy. In all cases the CSF was collected within 72 hours of injury. The CSF levels of neuron-specific enolase (NSE) and Aβ42 were measured using enzyme-linked immunosorbent assay. The levels of high-molecularweight β-amyloid oligomers were measured using Western blot analysis. Results. Patients with good outcomes showed an increase in the levels of CSF Aβ42 (p = 0.003). Those with bad outcomes exhibited an increase in CSF levels of β-amyloid oligomers (p = 0.009) and NSE (p = 0.001). In addition, the CSF oligomer levels correlated with the scores on the extended Glasgow Outcome Scale (r = -0.89, p = 0.0001), disability rating scale scores (r = 0.77, p = 0.005), CSF Aβ42 levels (r = -0.42, p = 0.12), and CSF NSE levels (r = 0.70, p = 0.004). Additionally, the receiver operating characteristic curve yielded an area under the curve for β-amyloid oligomers of 0.8750 ± 0.09. Conclusions. Detection of β-amyloid oligomers may someday become a useful clinical tool for determining injury severity and neurological outcomes in patients with TBI.

AB - Object. Traumatic brain injury (TBI) is known to be a risk factor for Alzheimer-like dementia. In previous studies, an increase in β-amyloid (A) monomers, such as β-amyloid 42 (Aβ42), in the CSF of patients with TBI has been shown to correlate with a decrease in amyloid plaques in the brain and improved neurological outcomes. In this study, the authors hypothesized that the levels of toxic high-molecular-weight β-amyloid oligomers are increased in the brain and are detectable within the CSF of TBI patients with poor neurological outcomes. Methods. Samples of CSF were collected from 18 patients with severe TBI (Glasgow Coma Scale Scores 3-8) and a ventriculostomy. In all cases the CSF was collected within 72 hours of injury. The CSF levels of neuron-specific enolase (NSE) and Aβ42 were measured using enzyme-linked immunosorbent assay. The levels of high-molecularweight β-amyloid oligomers were measured using Western blot analysis. Results. Patients with good outcomes showed an increase in the levels of CSF Aβ42 (p = 0.003). Those with bad outcomes exhibited an increase in CSF levels of β-amyloid oligomers (p = 0.009) and NSE (p = 0.001). In addition, the CSF oligomer levels correlated with the scores on the extended Glasgow Outcome Scale (r = -0.89, p = 0.0001), disability rating scale scores (r = 0.77, p = 0.005), CSF Aβ42 levels (r = -0.42, p = 0.12), and CSF NSE levels (r = 0.70, p = 0.004). Additionally, the receiver operating characteristic curve yielded an area under the curve for β-amyloid oligomers of 0.8750 ± 0.09. Conclusions. Detection of β-amyloid oligomers may someday become a useful clinical tool for determining injury severity and neurological outcomes in patients with TBI.

KW - Amyloid oligomers

KW - Amyloid-β42

KW - Biomarkers

KW - Cerebrospinal fluid

KW - Traumatic brain injury

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