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However, the impact of these factors on the functional connectivity of the entorhinal cortex (ERC) in clinically unpaired older adults (CUOA) with amyloid-\u03b2 (A\u03b2\u2009+) pathology remains unclear. A total of 1022 cognitively normal older adults with A\u03b2\u2009+\u2009(603 females and 586 APOE \u03b54\u2009+) from the Anti-Amyloid Treatment in Asymptomatic Alzheimer\u2019s (A4) study were included in this study. The 2\u2009\u00d7\u20092 (gender, 2 APOE genotypes) analysis of covariance was performed to compare the demographic information, cognitive performance, and volumetric MRI data among these groups. Voxel-wise comparisons of bilateral ERC functional connectivity (FC) were conducted, and partial correlation analyses were used to explore the associations between cognitive performance and ERC-FC strength. We found that the APOE genotype influenced ERC functional connectivity mainly in the sensorimotor network (SMN). Males exhibited higher ERC-FC in the salience network (SN), while females displayed higher ERC-FC in the default mode network (DMN), executive control network (ECN), and reward network. The interplay of sex and APOE genotype on ERC-FC was observed in the SMN and cerebellar lobe. The ERC-FC was associated with executive function and memory performance in individuals with CUOA-A\u03b2\u2009+\u2009. Our findings provide evidence of sex-specific ERC functional connectivity compensation mechanism in cognitively normal older adults with A\u03b2\u2009+\u2009pathology. This study may contribute to a better understanding of the mechanisms underlying the early stages of AD and may help develop personalized interventions in preclinical AD.<\/jats:p>","DOI":"10.1007\/s12035-024-04243-z","type":"journal-article","created":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T02:01:22Z","timestamp":1718244082000},"page":"475-484","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sex-Specific Entorhinal Cortex Functional Connectivity in Cognitively Normal Older Adults with Amyloid-\u03b2 Pathology"],"prefix":"10.1007","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9807-8049","authenticated-orcid":false,"given":"Liang","family":"Gong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyi","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunhua","family":"Xi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,6,13]]},"reference":[{"issue":"5580","key":"4243_CR1","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1126\/science.1072994","volume":"297","author":"J Hardy","year":"2002","unstructured":"Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer\u2019s disease: progress and problems on the road to therapeutics. 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