Detection of ß-amyloid oligomers as a predictor of neurological outcome after brain injury.

Journal of Neurosurgery

PubMedID: 23540266

Gatson JW, Warren V, Abdelfattah K, Wolf S, Hynan LS, Moore C, Diaz-Arrastia R, Minei JP, Madden C, Wigginton JG. Detection of ß-amyloid oligomers as a predictor of neurological outcome after brain injury. J Neurosurg. 2013;118(6):1336-42.
OBJECT
Traumatic brain injury (TBI) is known to be a risk factor for Alzheimer-like dementia. In previous studies, an increase in ß-amyloid (Aß) monomers, such as ß-amyloid 42 (Aß42), 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 ß-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 Aß42 were measured using enzyme-linked immunosorbent assay. The levels of high-molecular-weight ß-amyloid oligomers were measured using Western blot analysis.

RESULTS
Patients with good outcomes showed an increase in the levels of CSF Aß42 (p = 0.003). Those with bad outcomes exhibited an increase in CSF levels of ß-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 Aß42 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 ß-amyloid oligomers of 0.8750 ± 0.09.

CONCLUSIONS
Detection of ß-amyloid oligomers may someday become a useful clinical tool for determining injury severity and neurological outcomes in patients with TBI.