Apolipoprotein E genotype modulates longitudinal atrophy at the temporal lobe after mild traumatic brain injury

Backgrounds Moderate or severe traumatic brain injury (TBI) is one of the strongest environmental risks for late-life dementia, especially Alzheimer’s disease (AD). However, the interaction between genetic factors and environmental exposure to mild TBI triggering neurodegenerative processes is still unclear. We used longitudinal imaging to differentiate spatial patterns of progressive brain volume loss in individual patients with and without carrying apolipoprotein E (APOE) ε4 carriers. Methods For 59 patients with acute mild TBI (mTBI, age: 36.92 ± 11.91 years; 14 APOE ε4 carriers) and 48 matched healthy controls (HCs, age: 37.92 ± 11.72 years; 10 APOE ε4 carriers), longitudinal (6-12 months follow-up) brain structure was assessed using voxel-based morphometry on T1-weighted scans. Longitudinal volume changes in the temporal lobe were characterized by the Jacobian determinant (JD) metric, reflecting spatial warping between the baseline and follow-up scans. JD values were regionally calculated and correlated with neuropsychological measures. Results MTBI patients lost a mean of 0.27% (SD = 0.43) of GM and 0.27% (SD = 0.50) of WM volume in the temporal lobe over the 6-12 month follow-up. Patients with a high genetic risk for AD (APOE ε4 allele carries) were associated with severer atrophy in the left superior temporal gyrus and middle temporal gyrus regions than the controls ( P < 0.05). Furthermore, atrophy in these regions of gray matter could predict the performance change ratio of the language fluency in mTBI APOE ε4 carriers ( β = 0.570, P < 0.05). While, compared with HC APOE ε4 non-carriers, mTBI non-carriers exhibited volume loss in the medial temporal lobe. Conclusions This prospective study provided evidence that the APOE ε4 allele interacting with mTBI increased the risk of AD phenotype development with language dysfunction. ![Figure][1] ### Competing Interest Statement The authors have declared no competing interest. [1]: pending:yes