ABSTRACT
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.
