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Bioinform."],"abstract":"<jats:p>\n                    Perioperative neurocognitive disorders (PND) include postoperative delirium within 7 days after surgery, delayed neurocognitive recovery up to 30 days, and postoperative neurocognitive disorder up to 12 months. These outcomes are related, but they are not the same. They arise from the interaction of baseline brain vulnerability and perioperative stress, including inflammation, vascular instability, blood\u2013brain barrier injury, metabolic strain, and reduced neural reserve. Preoperative genetic profiling is useful because it can estimate latent susceptibility before surgery. Among current signals,\n                    <jats:italic>APOE<\/jats:italic>\n                    is the strongest and most biologically relevant locus. At the same time, Alzheimer\u2019s disease polygenic risk scores (AD-PRS) can capture non-\n                    <jats:italic>APOE<\/jats:italic>\n                    common-variant burden across lipid transport, endosomal trafficking, innate immune signaling, complement activity, microglial regulation, mitochondrial stress, and neurovascular integrity. Recent perioperative cohort studies have begun to test preoperative APOE-based and polygenic neurocognitive risk in surgical patients. Large delirium genetics studies also show a strong signal at the\n                    <jats:italic>APOE<\/jats:italic>\n                    locus and support overlap between delirium risk and Alzheimer\u2019s disease-related common-variant architecture. These findings support an APOE-aware framework in which\n                    <jats:italic>APOE<\/jats:italic>\n                    genotype is modeled separately from non-\n                    <jats:italic>APOE<\/jats:italic>\n                    AD-PRS. In clinical use, this genomic layer should be combined with baseline cognition, frailty, vascular comorbidity, surgery-related risk, and circulating biomarkers such as neurofilament light chain. This review summarizes the loci, molecular pathways, and translational model designs that can move preoperative genomic profiling from association to perioperative risk stratification.\n                  <\/jats:p>","DOI":"10.3389\/fbinf.2026.1829278","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T22:10:26Z","timestamp":1778537426000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Preoperative APOE and Alzheimer\u2019s disease polygenic risk profiling for perioperative neurocognitive disorders"],"prefix":"10.3389","volume":"6","author":[{"given":"Mengquan","family":"Tan","sequence":"first","affiliation":[{"name":"Institute of Rehabilitation Industry, Fujian University of Traditional Chinese Medicine","place":["Fuzhou, Fujian, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiling","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Nazareth Hospital","place":["Philadelphia, PA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huixian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Montefiore Medical Center, Albert Einstein College of Medicine","place":["New York, NY, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shilin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biology, Duke University","place":["Durham, NC, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meiling","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of General Practice, The Third People\u2019s Hospital of Shenzhen","place":["Shenzhen, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tongyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Diseases, Shanghai Jiao Tong University Affiliated Sixth People\u2019s Hospital","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, The University of Texas MD Anderson Cancer Center","place":["Houston, TX, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaling","family":"Dai","sequence":"additional","affiliation":[{"name":"Institute of Rehabilitation Industry, Fujian University of Traditional Chinese Medicine","place":["Fuzhou, Fujian, China"]},{"name":"Fujian Key Laboratory of Aptamers Technology, Fuzhou General Teaching Hospital (The 900th Hospital), Fujian University of Traditional Chinese Medicine","place":["Fuzhou, Fujian, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyuan","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Montefiore Medical Center, Albert Einstein College of Medicine","place":["Bronx, NY, United States"]},{"name":"Department of Neuroscience, Baylor College of Medicine","place":["Houston, TX, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"647974","DOI":"10.3389\/fnins.2021.647974","article-title":"ABCA7 regulates brain fatty acid metabolism during LPS-induced acute inflammation","volume":"15","author":"Aikawa","year":"2021","journal-title":"Front. 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