Effects of APOE ε2 on the Fractional Amplitude of Low-Frequency Fluctuation in Mild Cognitive Impairment: A Study Based on the Resting-State Functional MRI.

Background Apolipoprotein E (APOE) e2 is a protective genetic factor for Alzheimer's disease (AD). However, the potential interaction effects between the APOE e2 allele and disease status on the intrinsic brain activity remain elusive. Methods We identified 73 healthy control (HC) with APOE e3/e3, 61 mild cognitive impairment (MCI) subjects with APOE e3/e3, 24 HC with APOE e2/e3, and 10 MCI subjects with APOE e2/e3 from the ADNI database. All subjects underwent a resting-state functional MRI and Fluoro-deoxy-glucose positron emission tomography (FDG-PET). We used a fractional amplitude of low-frequency fluctuation (fALFF) to explore the spontaneous brain activity. Based on the mixed-effects analysis, we explored the interaction effects between the APOE e2 allele versus disease status on brain activity and metabolism in a voxel-wise fashion (GRF corrected, p < 0.01), followed by post hoc two-sample t-tests (Bonferroni corrected, p < 0.05). We then investigated the relationship between the mean imaging metrics and cognitive abilities. Results There are no significant differences in gender, age, or education among the four groups. The interaction effect on brain activity was located in the inferior parietal lobule (IPL). Post hoc analysis showed that APOE e2/e3 MCI had an increased IPL fALFF than APOE e3/e3 MCI. Regarding the APOE e2 allele effects, we found that e2 carriers had a decreased fALFF in the transverse temporal gyrus than non-carriers. Also, FDG-PET results showed a lower SUVR of the frontal lobe in APOE e2 carriers than non-carriers. Furthermore, fALFF of IPL was correlated with the visuospatial function (r = -0.16, p < 0.05). Conclusion APOE e2 carriers might have a better brain reservation when coping with AD-related pathologies.