ObjectiveApolipoprotein E isoform (E4) has been posited to affect outcomes after central nervous system injury. This project sought to determine the relationship between the apoE4 allele and the recovery of amino acid neurotransmitters (aspartate, glutamate, and lactate/pyruvate ratio [L/P]) following a traumatic brain injury (TBI) after controlling for patient characteristics.DesignThis prospective clinical study examined neurotransmitters and L/P within the cerebrospinal fluid and compared the trends by apoE genotypes.SettingAdults with TBI were recruited from a neurotrauma intensive care unit within a trauma I university medical center.PatientsNinety-one patients were enrolled into the study after a severe TBI (Glasgow Coma Scale [GCS] score, ≤8). Cerebrospinal fluid was serially sampled from a ventriculostomy every 4 hrs for the first 24 hrs and every 6 hrs for 25–120 hrs after injury.Measurements and Main ResultsHierarchical linear modeling analyses were used to compare the change of glutamate, aspartate, and L/P over time by the presence or absence of the apoE4 allele, with GCS score, sex, race, and therapeutic hypothermias included as covariates. There was a significant apoE4 allele group effect on both the linear and quadratic slopes in aspartate. In glutamate, the rate of change in glutamate was statistically related to GCS score. There was no significant difference in the glutamate response over time by the presence of the apoE4 allele. There was a significant difference in the change in L/P across time, with faster recovery when the apoE4 allele was absent.ConclusionsRecovery of aspartate and L/P differed depending on the presence of the apoE4 allele. Patients with the allele had significant increased and sustained levels of aspartate and L/P after TBI. Changes in glutamate were related to severity of illness and were independent of the presence of the apoE4 allele.