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We also exposed induced pluripotent stem cell-derived neurons to ISRIB and chloroquine. Conversely, we mitigated protein stress with rapamycin. We assessed intervention impact on\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Increasing protein stress elevated and decreasing protein stress lowered\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      expression. In SH-SY5Y cells rapamycin blocked oligomycin-induced mTOR 2448 phosphorylation, Akt 473 phosphorylation, and\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      expression. In chloroquine-treated neurons rapamycin reduced mTOR phosphorylation and\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Protein stress initiates\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      expression and facilitates mitochondrial dysfunction's impact on\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      by engaging the mTOR pathway. Our findings link aging and AD biology.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261452598","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T07:44:24Z","timestamp":1779349464000},"page":"714-727","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["An aging hallmark, Alzheimer's disease, and\n                    <i>APOE<\/i>\n                    nexus"],"prefix":"10.1177","volume":"112","author":[{"given":"Alexander P.","family":"Gabrielli","sequence":"first","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center, University of Kansas, Fairway, KS, USA"},{"name":"University of Kansas Medical 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