{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:13:34Z","timestamp":1791821614780,"version":"4.3.4"},"reference-count":71,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["GeroScience"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Alzheimer\u2019s disease (AD) disproportionately affects women and carriers of the apolipoprotein E \u03b54 allele (APOE4), yet little is known about how sex and APOE interact to influence white matter (WM) integrity during disease progression. We integrated diffusion MRI and matched blood transcriptomic data to investigate these interactions and their underlying biological mechanisms. WM microstructure was quantified using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), and regional vulnerability was assessed with a composite vulnerability score (CVS) derived from associations between diffusion features and AD severity across clinical traits in each of the four sex-APOE groups (female or male, with or without APOE4). Brain parcellation with the Eve atlas revealed regions consistently affected across sex-APOE groups (e.g., parahippocampal and superior temporal gyri) and regions specific to individual groups (e.g., the cingulum in females with APOE4 and the middle frontal gyrus in males without APOE4). Gene co-expression network analysis of the\u00a0matched blood expression data identified gene\u00a0subnetworks linked to group-specific regional vulnerability, including a muscle tissue morphogenesis module regulated by\n                    <jats:italic>NEURL1B<\/jats:italic>\n                    and\n                    <jats:italic>HIST1H2BN<\/jats:italic>\n                    associated with middle frontal gyrus vulnerability. These findings demonstrate that sex and APOE genotype jointly shape region-specific WM vulnerability and its molecular signatures in AD. Understanding these interactions provides novel mechanistic insights and may inform precision approaches to drug development, biomarker discovery, and clinical trial design for AD.\n                  <\/jats:p>","DOI":"10.1007\/s11357-025-02089-4","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:27:27Z","timestamp":1771460847000},"page":"8591-8608","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Sex and APOE genotype specific brain regional vulnerability to Alzheimer's 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