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A total of 752 participants with a clinical etiologic diagnosis of AD were selected from the National Alzheimer's Coordinating Center (NACC) database. Bayesian multilevel regression was used to examine both the within\u2010 and between\u2010sex differences in gray\u2010matter cortical thickness and total NPS burden associated with <jats:italic>APOE<\/jats:italic> homozygosity. Female homozygote carriers displayed a high probability of having reduced cortical thickness primarily in medial\u2013lateral temporal regions and a greater burden of NPS, relative to both non\u2010homozygous females and homozygous males. These findings support the notion that <jats:italic>APOE4<\/jats:italic> status affects cortical thickness and symptom burden in men and women with AD differentially, with females showing more pronounced effects in brain areas known to be vulnerable in early AD. Future investigations should attempt to elucidate the proposed pattern of decline longitudinally.<\/jats:p>","DOI":"10.1002\/ajmg.b.33008","type":"journal-article","created":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T05:34:52Z","timestamp":1727760892000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Sex Differences in Cortical Thickness and Neuropsychiatric Symptom Burden Based on <i>APOE4<\/i> Homozygosity in Alzheimer's Disease"],"prefix":"10.1002","volume":"198","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5863-6974","authenticated-orcid":false,"given":"Marc A.","family":"Khoury","sequence":"first","affiliation":[{"name":"Keenan Research Centre for Biomedical Science, the Li Ka Shing Knowledge Institute St. Michael's Hospital  Toronto Ontario Canada"},{"name":"Temerty Faculty of Medicine Institute of Medical Science, University of Toronto  Toronto Ontario 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