Apolipoprotein E polymorphism affects brain functional connectivity density in healthy young adults: a resting-state functional MRI

Abstract

Objective To explore the aberrance of brain activity in healthy young adults with apolipoprotein E (APOE) e2, e3 and e4 allele by the method of functional connectivity density (FCD) . Method Two hundred and thirteen young healthy adults underwent the 3 T resting-state functional MRI, the neuropsychological tests and genotype testing for e2, e3 and e4 allele. Age -and gender-matched individuals, including 14 subjects with APOE e2, 31 subjects with APOE e4 and 31 subjects with APOE e3 were enrolled for final analysis. FCD mapping was used to compare the brain functional connective networks among the three groups. All results were corrected with a Gaussian random field (GRF) (voxel-level of P<0.01 and joint cluster-level of P<0.05) . Correlation analysis was performed between abnormal short -and long-range FCD values and neuropsychological scores. Results Compared with APOE e3 carriers, the short -and long-range FCD values of APOE e2 carriers were increased in the frontal lobe, particularly in the medial prefrontal lobe (37 voxels, t=3.54) , anterior cingulate cortex (36 voxels, t=3.19) and orbital frontal cortex (41 voxels, t=3.72) , while APOE e4 carriers showed decreased short-range FCD in the bilateral cuneus (38 voxels, t=-3.68) . Moreover, the long-range FCD values of APOE e4 group were decreased in right orbital frontal cortex (46 voxels, t=-4.56) and increased in the right inferior parietal lobe (31 voxels, t=3.49) compared with that of APOE e2 group. No significant correlation was detected with Bonferroni correction. Conclusions The opposite FCD alteration in cuneus and inferior parietal lobe might be the early existence of inhibitory and compensatory mechanism modulated by the e4 allele in the young age, while the increased FCD in frontal lobe might be the underlying protective mechanism of delaying the onset of Alzheimer's disease. Key words: APOE polymorphism; Functional connectivity density; Alzheimer disease