APOE polymorphism affects brain default mode network in healthy young adults: A STROBE article

Abstract

To investigate the effect of apolipoprotein E (APOE) gene polymorphism on the resting-state brain function, structure, and blood flow in healthy adults younger than 35 years, using multimodality magnetic resonance (MR) imaging. Seventy-six healthy adults (34 men, 23.7±2.8 y; 31 APOE e4/e3 carriers, 31 e3/e3 carriers, and 14 e2/e3 carriers)were included. For restingstate functionalMRI data, default mode network (DMN) and amplitude of low-frequency fluctuationmapswere extracted and analyzed.Voxel-based morphometry, diffusion tensor imaging from structural imaging, and cerebral blood flow based on arterial spin labeling MR imaging were also analyzed. Correlation analysis was performed between the above mentioned brain parameters and neuropsychological tests. There were no differences in neuropsychological performances, amplitude of low-frequency fluctuation, gray/white matter volumes, fractional anisotropy, mean diffusivity, or whole brain cerebral blood flow among the 3 groups. As for DMN, the e4/e3 group showed increased functional connectivities (FCs) in the left medial prefrontal cortex and bilateral posterior cingulate cortices/precuneus compared with the e3/e3 group, and increased FCs in the left medial prefrontal cortex and right temporal lobe compared with the e2/e3 group (P<0.05, Alphasim corrected). No differences of DMN FCs were found between the e2/e3 and e3/e3 groups. FCs in the right temporal lobe positively correlated with the performances of vocabulary learning, delayed recall, and graph recall in all participants (P<0.05). APOE e4 carriers exhibited significantly increased DMN FCs when compared with e3 and e2 carriers. The e4 affects DMN FCs before brain structure and blood flow in cognitively intact young patients, suggesting DMN FC may serve as a potential biomarker for the detection of early manifestations of genetic effect.