APOE4 and age affect the brain entorhinal cortex structure and blood arachidonic acid and docosahexaenoic acid levels after mild TBI.

A reduction in the thickness and volume of the brain entorhinal cortex (EC), together with changes in blood arachidonic acid (AA) and docosahexaenoic acid (DHA), are associated with Alzheimer's disease (AD) among apolipoprotein E ε4 carriers. Magnetic Resonance Imaging (n = 631) and plasma lipidomics (n = 181) were performed using the LIMBIC/CENC cohort to examine the influence of ε4 on AA- and DHA-lipids and EC thickness and volume in relation to mild traumatic brain injury (mTBI). Results showed that left EC thickness was higher among ε4 carriers with mTBI. Repeated mTBI (r-mTBI) was associated with reduced right EC thickness after controlling for ε4, age and sex. Age, plus mTBI chronicity were linked to increased EC White Matter Volume (WMV). After controlling for age and sex, the advancing age of ε4 carriers with blast mTBI was associated with reduced right EC Grey Matter Volume (GMV) and thickness. Among ε4 carriers, plasma tau and Aβ40 were associated with mTBI and blast mTBI, respectively. Chronic mTBI, ε4 and AA to DHA ratios in phosphatidylcholine, ethanolamides, and phosphatidylethanolamine were associated with decreased left EC GMV and WMV. Further research is needed to explore these as biomarkers for detecting AD pathology following mTBI.