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

Figures

• 

  Fig. 1. Influence of the ε4 allele on mTBI and blast injuries on thickness and volume of the EC. (A-D) Means ± SE (A) Left EC thickness stratified by the presence of the ε4 allele and mTBI diagnosis (ε4- control = 95, ε4 + controls = 33, ε4- mTBI = 375 and ε4 + mTBI = 128). Among controls, the thickness of the left EC was smaller among ε4 carriers compared to non-ε4 carriers. Compared to ε4 controls, ε4 + mTBI patients had higher left EC thickness. (B) There were no significant differences between mTBI patients and controls and no influence of the ε4 status on the right EC thickness. (C) Left GMW stratified by the presence of the ε4 allele and blast mTBI (ε4- non-blast = 318, ε4 + non-blast (including healthy controls and those without blast-related mTBI) = 106, ε4- blast = 183, ε4 + blast = 60). There were no differences between the groups. (D) Compared to the ε4 + non-blast group, ε4 + patients with blast mTBI had higher GMV in the right EC. *p < 0.05 for ANOVA followed by B-H correction. (E–F) Heatmaps showing beta-coefficients from linear regression analyses. (E) The interaction between the presence of the ε4 allele and an increase in the number of blast mTBI per participant was…

• 

  Fig. 2. Association of protein and lipid biomarkers with mTBI diagnosis. Each image is a heat map of odds ratios and corresponding p-values for each protein and AA and DHA ratios of each lipid class. (A) Logistic regression controlling for the independent effects of age, sex, and ε4 as well as incorporating interactive effects of each protein (tau, Aβ40, Aβ42, Aβ40/Aβ42 ratios and NfL) with ε4 and with ε4 plus age were performed to calculate the OR for estimating their association with a diagnose of mTBI. While plasma total tau in the presence of the ε4 allele is associated with a mTBI diagnosis. The OR for the mTBI diagnosis is < 1 for the interaction between age, ε4 and each of the proteins above. (B) Interactions between ε4 and AA to DHA ratios in PC, PE, CE, and EA were associated with a significantly higher OR for the diagnosis of mTBI. As with protein biomarkers, interactions between age, ε4 and AA to DHA ratios in these lipid classes resulted in OR < 1 for a diagnosis of mTBI.

• 

  Fig. 3. The ratios of AA to DHA in lipid classes, when combined with the years since 1st mTBI among ε4 carriers, are associated with differences in the EC thickness and volume. (A-E) Heatmaps showing beta-coefficients from linear regression modeling examining associations of the brain EC thickness and volume with different AA to DHA ratios and their interactions with years since 1st mTBI and ε4. (A) Increasing AA to DHA ratios within the EA lipid class with increasing years since 1st mTBI among ε4 carriers are positively associated with the GMV within the left EC. (B-D) There were no associations between AA to DHA ratios within DG, CE and PE and the brain EC thickness and volume. (E) Increasing AA to DHA ratios in PC with increasing years since 1st mTBI among ε4 carriers are associated with the GMV in the left EC. *p < 0.05.

• 

  Fig. 4. Components 2 and 3 of PCA associated with r-mTBI predicted EC thickness and volume. Logistic regression analyses evaluated the individual and combined influence of PCA Component 2 with mTBI diagnosis and the presence of the ε4 allele on the odds of having lowered thickness and the volume of the EC. (A) Among ε4 carriers, PCA component 2, consisting of primarily AA and DHA-containing species in PC and PE along with DHA-containing species from CE and EA and AA-containing DG species, were associated with increased odds of having low GMV within the right EC, but the lower odds of GWV among those with ε4 and r-mTBI. (B) Among ε4 carriers with r-mTBI, PCA Component 3 containing AA and DHA species within PC and PE were associated with increased odds of having low WMV within the left EC. None of the PCAs were associated with the thickness of either the left or the right EC. *p < 0.05.

• 

  Fig. 5. A summary illustration of the hypothesis for mTBI and APOE-mediated AD risk and onset. The left panel of the image shows that mTBI, APOE and AA to DHA balance can independently present as AD risk. The right panel shows how these factors interact to precipitate the onset of AD.