Preliminary results on the impact of apoe genotypes on cerebrospinal fluid (CSF) excitatory amino acids (EAA) and metabolites in traumatic brain injured (TBI) adults

Document Type

Journal Article

Publication Date



Critical Care Medicine








Introduction: Apolipoprotein E (APOE) genotype has been linked to beta amyloid deposits and a microtubule-associated protein, tau, in an isoform-specific manner. APOE4 may impair neuronal growth potentially impairing recovery following injury.1 Wilson et al2 reported that patients with APOE4 alleles had poorer verbal memory and psychomotor slowing following injury when compared to patients without APOE4 alleles. The purpose of this project was to determine whether the trajectory of EAA and lactate/pyruvate ratio was altered based on APOE-genotype following a TBI. Methods: The APOE genotypes were identified in 24 adults by genonmic DNA amplification followed by digestion with HhaI restriction enzyme. Serial CSF samples from a ventriclostomy catheter placed within the right ventricle were removed by gravity drainage every 12 hours for the First 72 hours after injury. Samples were immediately placed into a freezer at -80 degrees C for storage. Aspartate and glutamate were measured using high-pressure liquid chromatography (HPLC) with fluorescence detection. Lactate and pyruvate were measured using ultraviolet detection. Results: Of the 24 subjects, 6 had APOE 2/3 genotype, 12 had APOE 3/3 genotype and 6 had APOE 3/4 genotype. Aspartate ranged from .06 to 3.34 (M=.6083; SD=.59); glutamate ranged from 71.1 to 722.8 (M=158.36; SD=119.6) and the L/P ratio ranged from 8.22 to 75.62 (M=28.19; SD=12.8). Patients were grouped based on the presence or absence of APOE4 allele. Using a repeated measure analysis of variance, significant differences existed across time in aspartate, glutamate and L/P ratio. Aspartate and glutamate levels were elevated in patients carrying the APOE4 allele. Conclusions: The results of this study suggest that the presence of the APOE4 allele is related to enhanced levels of EAA (glutamate and asparate) which contribute to secondary damage following TBI. The mechanism of this relationship is not known and warrants further study.

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