title: Detection of β-amyloid oligomers as a predictor of neurological outcome after brain injury.
abstract: OBJECTIVE
  Traumatic brain injury (TBI) is known to be a risk factor for Alzheimer-like dementia. In previous studies, an increase in β-amyloid (Aβ) 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-molecular-weight 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.
authors.affiliation: Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9160, USA. joshua.gatson@utsw.edu
authors.forename: Joshua Wayne
authors.initials: JW
authors.lastname: Gatson
authors.forename: Victoria
authors.initials: V
authors.lastname: Warren
authors.forename: Kareem
authors.initials: K
authors.lastname: Abdelfattah
authors.forename: Steven
authors.initials: S
authors.lastname: Wolf
authors.forename: Linda S
authors.initials: LS
authors.lastname: Hynan
authors.forename: Carol
authors.initials: C
authors.lastname: Moore
authors.forename: Ramon
authors.initials: R
authors.lastname: Diaz-Arrastia
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Minei
authors.forename: Christopher
authors.initials: C
authors.lastname: Madden
authors.forename: Jane G
authors.initials: JG
authors.lastname: Wigginton
mesh_terms: D000293:Adolescent; D000328:Adult; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000503:physiopathology; D001930:Brain Injuries / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000503:physiopathology; D005260:Female; D015600:Glasgow Coma Scale; D006801:Humans; D008297:Male; D008875:Middle Aged; D009841:Oligonucleotides / Q000134:cerebrospinal fluid*; D010751:Phosphopyruvate Hydratase / Q000134:cerebrospinal fluid; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D009841:Oligonucleotides; D010751:Phosphopyruvate Hydratase