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. 2021 Apr 29:13:591347.
doi: 10.3389/fnagi.2021.591347. eCollection 2021.

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

Xiaocao Liu  1 , Qingze Zeng  1 , Xiao Luo  1 , Kaicheng Li  1 , Hui Hong  1 , Shuyue Wang  1 , Xiaojun Guan  1 , Jingjing Wu  1 , Ruiting Zhang  1 , Tianyi Zhang  2 , Zheyu Li  2 , Yanv Fu  2 , Tao Wang  1 , Chao Wang  1 , Xiaojun Xu  1 , Peiyu Huang  1 , Minming Zhang  1 ; Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Affiliations

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

Xiaocao Liu et al. Front Aging Neurosci. .

Abstract

Background: 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.

Methods: 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, 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 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 (r = -0.16, p < 0.05).

Conclusion: APOE ε2 carriers might have a better brain reservation when coping with AD-related pathologies.

Keywords: APOE; Alzheimer’s disease; fractional amplitude of low-frequency fluctuation; mild cognitive impairment; resting-state functional MRI.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The decreased fractional amplitude low-frequency fluctuations (fALFF) was found in the transverse temporal gyrus in the APOE ε2/ε3 carriers groups compared to the APOE ε3/ε3 carriers’ groups. The statistical threshold was set at p < 0.01 with a cluster-level p < 0.05 (two-tailed, GRF corrected).
FIGURE 2
FIGURE 2
The increased fractional amplitude low-frequency fluctuations (fALFF) were found in the inferior parietal lobule (IPL) among healthy controls (HC) with APOE ε3/ε3, HC with APOE ε2/ε3, mild cognitive impairment (MCI) with APOE ε3/ε3, and MCI with APOE ε2/ε3. The results were obtained by analysis of covariance (ANCOVA) analysis adjusted with GM [p < 0.01, cluster level < 0.05, two-tailed, Gaussian random field (GRF) correction].
FIGURE 3
FIGURE 3
The “APOE × disease” (interaction) effects between APOE and cognitive status were shown. In addition, the average fALFF values in the IPL of groups were demonstrated. *Represents p < 0.05 between MCI and HC. #Represents p < 0.05 between APOE ε3/ε3 and APOE ε2/ε3 in MCI.
FIGURE 4
FIGURE 4
The APOE ε2/ε3 carriers groups had a slight decreased standard uptake value ratio (SUVR) of FDG-PET in the Frontal Lobe compared to the APOE ε3/ε3 homozygote groups. The statistical threshold was set at p < 0.01 with a cluster-level of p < 0.05 (two-tailed, GRF corrected).
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