{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:04:09Z","timestamp":1753891449280,"version":"3.41.2"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T00:00:00Z","timestamp":1619654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Apolipoprotein E (APOE) \u03b52 is a protective genetic factor for Alzheimer\u2019s disease (AD). However, the potential interaction effects between the APOE \u03b52 allele and disease status on the intrinsic brain activity remain elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We identified 73 healthy control (HC) with APOE \u03b53\/\u03b53, 61 mild cognitive impairment (MCI) subjects with APOE \u03b53\/\u03b53, 24 HC with APOE \u03b52\/\u03b53, and 10 MCI subjects with APOE \u03b52\/\u03b53 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 \u03b52 allele versus disease status on brain activity and metabolism in a voxel-wise fashion (GRF corrected, <jats:italic>p<\/jats:italic> &amp;lt; 0.01), followed by <jats:italic>post hoc<\/jats:italic> two-sample <jats:italic>t<\/jats:italic>-tests (Bonferroni corrected, <jats:italic>p<\/jats:italic> &amp;lt; 0.05). We then investigated the relationship between the mean imaging metrics and cognitive abilities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats: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). <jats:italic>Post hoc<\/jats:italic> analysis showed that APOE \u03b52\/\u03b53 MCI had an increased IPL fALFF than APOE \u03b53\/\u03b53 MCI. Regarding the APOE \u03b52 allele effects, we found that \u03b52 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 \u03b52 carriers than non-carriers. Furthermore, fALFF of IPL was correlated with the visuospatial function (<jats:italic>r<\/jats:italic> = \u22120.16, <jats:italic>p<\/jats:italic> &amp;lt; 0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>APOE \u03b52 carriers might have a better brain reservation when coping with AD-related pathologies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2021.591347","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T10:29:41Z","timestamp":1619692181000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Effects of APOE \u03b52 on the Fractional Amplitude of Low-Frequency Fluctuation in Mild Cognitive Impairment: A Study Based on the Resting-State Functional MRI"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiaocao","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingze","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaicheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuyue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojun","family":"Guan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruiting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianyi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanv","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peiyu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minming","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI)","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.jalz.2011.03.008","article-title":"The diagnosis of mild cognitive impairment due to Alzheimer\u2019s disease: recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease.","volume":"7","author":"Albert","year":"2011","journal-title":"Alzheimers Dement."},{"key":"B2","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1212\/01.wnl.0000343853.00346.a4","article-title":"APOE epsilon2 is associated with intact cognition but increased Alzheimer pathology in the oldest old.","volume":"72","author":"Berlau","year":"2009","journal-title":"Neurology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1038\/nn.2801","article-title":"Neuronal activity regulates the regional vulnerability to amyloid-beta deposition.","volume":"14","author":"Bero","year":"2011","journal-title":"Nat. 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