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Dysregulation of the mammalian target of rapamycin (mTOR) and insulin (INS) signaling pathways has been reported in DS. We hypothesized that upstream alterations in these two pathways contribute to hippocampal dysfunction in DS\u2010AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We used spatial transcriptomics and localized proteomic techniques to examine mTOR\/INS signaling pathways in subregions of the hippocampus in\n                      <jats:italic>post mortem<\/jats:italic>\n                      tissue from individuals with DS\u2010AD and age\u2010matched neurotypical controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>mTOR pathways were significantly altered in specific hippocampal subfields in DS\u2010AD, and INS pathways were significantly altered in dentate granule neurons.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These preliminary spatial transcriptomics and localized proteomics findings demonstrate an interplay between select hippocampal mTOR\/INS pathways and cellular populations, suggesting potential novel drug targets and early biomarkers for DS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71776","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:35:37Z","timestamp":1787567737000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Disruption of hippocampal upstream regulators of mTOR and insulin pathways in Down syndrome with Alzheimer's disease neuropathology: Preliminary observations"],"prefix":"10.1002","volume":"22","author":[{"given":"Abigail J.","family":"Nordbeck","sequence":"first","affiliation":[{"name":"Department of Neurosurgery University of 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LLC  Sheridan Wyoming USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric D.","family":"Hamlett","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Laboratory Medicine Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Head","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of California Irvine  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliott J.","family":"Mufson","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience and Neurology Barrow Neurological Institute  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia E.","family":"Perez","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience and Neurology Barrow Neurological 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