{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:53:49Z","timestamp":1792032829754,"version":"4.4.0"},"reference-count":84,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2020,10,31]],"date-time":"2020-10-31T00:00:00Z","timestamp":1604102400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer's Disease Reports"],"published-print":{"date-parts":[[2020,12,28]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Brain insulin resistance and deficiency are well-recognized abnormalities in Alzheimer\u2019s disease (AD) and likely mediators of impaired energy metabolism. Since apolipoprotein E ( APOE) is a major risk factor for late-onset AD, it was of interest to examine its potential contribution to altered insulin-linked signaling networks in the brain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>The main goal was to evaluate the independent and interactive contributions of AD severity and APOE \u025b4 dose on brain expression of insulin-related polypeptides and inflammatory mediators of metabolic dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Postmortem fresh frozen frontal lobe tissue from banked cases with known APOE genotypes and different AD Braak stages were used to measure insulin network polypeptide immunoreactivity with a commercial multiplex enzyme-linked immunosorbent assay (ELISA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Significant AD Braak stage and APOE genotype-related abnormalities in insulin, C-peptide, gastric inhibitory polypeptide (GIP), glucaton-like peptide-1 (GLP-1), leptin, ghrelin, glucagon, resistin, and plasminogen activator inhibitor-1 (PAI-1) were detected. The main factors inhibiting polypeptide expression and promoting neuro-inflammatory responses included AD Braak stage and APOE \u025b4\/ \u025b4 rather than \u025b3\/ \u025b4.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>This study demonstrates an expanded role for impaired expression of insulin-related network polypeptides as well as neuroinflammatory mediators of brain insulin resistance in AD pathogenesis and progression. In addition, the findings show that APOE has independent and additive effects on these aberrations in brain polypeptide expression, but the impact is decidedly greater for APOE \u025b4\/ \u025b4 than \u025b3\/ \u025b4.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/adr-200238","type":"journal-article","created":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T11:50:03Z","timestamp":1604404203000},"page":"479-493","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":17,"title":["Dysregulation of Insulin-Linked Metabolic Pathways in Alzheimer\u2019s Disease: Co-Factor Role of Apolipoprotein E\n                    <i>\u025b<\/i>\n                    4"],"prefix":"10.1177","volume":"4","author":[{"given":"James","family":"Robbins","sequence":"first","affiliation":[{"name":"Alpert Medical School of Brown University, Providence, RI, 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