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Apolipoprotein E (<jats:italic>APOE<\/jats:italic>) \u03b52 is a protective genetic factor in AD and MCI, and cholinergic sprouting depends on <jats:italic>APOE<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We investigated the effect of the <jats:italic>APOE<\/jats:italic> \u03b52 allele on BFCS functional connectivity (FC) in cognitively normal (CN) subjects and MCI patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We included 60 MCI patients with <jats:italic>APOE<\/jats:italic> \u03b53\/\u03b53, 18 MCI patients with <jats:italic>APOE<\/jats:italic> \u03b52\/\u03b53, 73 CN subjects with <jats:italic>APOE<\/jats:italic> \u03b53\/\u03b53, and 36 CN subjects with <jats:italic>APOE<\/jats:italic> \u03b52\/\u03b53 genotypes who had resting\u2010state functional magnetic resonance imaging data from the Alzheimer's disease Neuroimaging Initiative. We used BFCS subregions (Ch1\u20103 and Ch4) as seeds and calculated the FC with other brain areas. Using a mixed\u2010effect analysis, we explored the interaction effects of <jats:italic>APOE<\/jats:italic> \u03b52 allele \u00d7 cognitive status on BFCS\u2010FC. Furthermore, we examined the relationships between imaging metrics, cognitive abilities, and AD pathology markers, controlling for sex, age, and education as covariates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>An interaction effect on functional connectivity was found between the right Ch4 (RCh4) and left insula (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05, corrected), and between the RCh4 and left Rolandic operculum (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05, corrected). Among all subjects and <jats:italic>APOE<\/jats:italic> \u03b52 carriers, RCh4\u2010left Insula FC was associated with early tau deposition. Furthermore, no correlation was found between imaging metrics and amyloid burden. Among all subjects and <jats:italic>APOE<\/jats:italic> \u03b52 carriers, FC metrics were associated with cognitive performance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The <jats:italic>APOE<\/jats:italic> \u03b52 genotype may play a protective role during BFCS degeneration in MCI.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14038","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T10:10:50Z","timestamp":1670235050000},"page":"597-608","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effects of <i>APOE<\/i> \u03b52 allele on basal forebrain functional connectivity in mild cognitive impairment"],"prefix":"10.1111","volume":"29","author":[{"given":"Xiaocao","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Radiology The 2nd Affiliated Hospital of Zhejiang University School of Medicine  Hangzhou 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