AUTHOR=Liu Xiaocao , Zeng Qingze , Luo Xiao , Li Kaicheng , Hong Hui , Wang Shuyue , Guan Xiaojun , Wu Jingjing , Zhang Ruiting , Zhang Tianyi , Li Zheyu , Fu Yanv , Wang Tao , Wang Chao , Xu Xiaojun , Huang Peiyu , Zhang Minming ,  for the Alzheimer’s Disease Neuroimaging Initiative (ADNI) 

TITLE=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

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=13

YEAR=2021

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.591347

DOI=10.3389/fnagi.2021.591347

ISSN=1663-4365

ABSTRACT=<sec><title>Background</title><p>Apolipoprotein E (APOE) ε2 is a protective genetic factor for Alzheimer’s disease (AD). However, the potential interaction effects between the APOE ε2 allele and disease status on the intrinsic brain activity remain elusive.</p></sec><sec><title>Methods</title><p>We identified 73 healthy control (HC) with APOE ε3/ε3, 61 mild cognitive impairment (MCI) subjects with APOE ε3/ε3, 24 HC with APOE ε2/ε3, and 10 MCI subjects with APOE ε2/ε3 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 ε2 allele versus disease status on brain activity and metabolism in a voxel-wise fashion (GRF corrected, <italic>p</italic> &lt; 0.01), followed by <italic>post hoc</italic> two-sample <italic>t</italic>-tests (Bonferroni corrected, <italic>p</italic> &lt; 0.05). We then investigated the relationship between the mean imaging metrics and cognitive abilities.</p></sec><sec><title>Results</title><p>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). <italic>Post hoc</italic> analysis showed that APOE ε2/ε3 MCI had an increased IPL fALFF than APOE ε3/ε3 MCI. Regarding the APOE ε2 allele effects, we found that ε2 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 ε2 carriers than non-carriers. Furthermore, fALFF of IPL was correlated with the visuospatial function (<italic>r</italic> = −0.16, <italic>p</italic> &lt; 0.05).</p></sec><sec><title>Conclusion</title><p>APOE ε2 carriers might have a better brain reservation when coping with AD-related pathologies.</p></sec>