{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:30:35Z","timestamp":1792074635211,"version":"4.4.0"},"reference-count":69,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:00:00Z","timestamp":1740355200000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>\n                      Growing evidence suggests a connection between insulin resistance and\u00a0apolipoprotein E (\n                      <jats:italic>APOE<\/jats:italic>\n                      )\u00a0genotype in Alzheimer's disease (AD) pathogenesis, but the mechanisms\u00a0are unclear. We examined effects of insulin resistance and\n                      <jats:italic>APOE<\/jats:italic>\n                      genotype on blood\u2013brain barrier (BBB) integrity in AD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      BBB integrity was measured in 196 biologically\u2010confirmed non\u2010diabetic patients with AD evaluating CSF\/serum albumin ratio,\u00a0kappa and lambda free light chains (FLCs). Insulin resistance was assessed using triglyceride\u2013glucose index (TyG). The impact of TyG on BBB integrity, and its interaction with\n                      <jats:italic>APOE<\/jats:italic>\n                      genotypes, was\u00a0analyzed using multivariate models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Sixty\u2010four percent of patients with AD showed altered TyG, with the 21.8% classified as\u00a0high TyG. TyG\u00a0subgroups were associated with BBB abnormalities, with similar AD clinical and biomarkers profile. A significant interaction between TyG and\u00a0\n                      <jats:italic>APOE<\/jats:italic>\n                      \u00a0\u03b54\/\u03b54 genotype on BBB permeability was found in multivariate analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      Insulin resistance is a common feature in non\u2010diabetic AD and correlates with altered BBB permeability, interacting synergistically with\u00a0\n                      <jats:italic>APOE<\/jats:italic>\n                      \u00a0genotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            Insulin resistance and apolipoprotein E (\n                            <jats:italic>APOE<\/jats:italic>\n                            ) genotype are well\u2010recognized risk factors for Alzheimer's disease (AD).\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Insulin resistance shows high prevalence in patients with AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Insulin resistance is related to damage in blood\u2013brain barrier (BBB) integrity.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            The association between the triglyceride\u2013glucose (TyG) index and BBB permeability varies in relation to\n                            <jats:italic>APOE<\/jats:italic>\n                            genotype; patients with the\n                            <jats:italic>APOE<\/jats:italic>\n                            \u03b54\/\u03b54 displayed higher BBB permeability.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14556","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T22:35:14Z","timestamp":1741732514000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["The role of insulin resistance and\n                    <i>APOE<\/i>\n                    genotype on blood\u2013brain barrier integrity in Alzheimer's 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