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Despite extensive research, disease\u2010modifying therapies remain elusive. We integrated single\u2010cell RNA sequencing (scRNA\u2010seq), spatial transcriptomics, and in vitro validation to identify repurposable drugs for AD\n                      <jats:sup>1<\/jats:sup>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Computational drug repurposing was performed using cell\u2010type\u2010specific analysis of scRNA\u2010seq datasets from AD cortical regions. Trichostatin\u2010A (TSA) effects were validated in human induced pluripotent stem cells (iPSC) \u2010derived cortical neurons exposed to A\u03b2 oligomers. Cross\u2010dataset integration identified convergent therapeutic targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      TSA emerged as the top candidate, protecting neurons from A\u03b2 toxicity and preserving synaptic integrity.\n                      <jats:italic>DISC1<\/jats:italic>\n                      (Disrupted\u2010In\u2010Schizophrenia 1) was uniquely upregulated across TSA\u2010treated neurons, AD\u2010associated neuronal subpopulations, and protective microglial subtypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      <jats:italic>DISC1<\/jats:italic>\n                      represents a convergent therapeutic target for AD, mediating TSA's neuroprotective effects through pathways regulating\n                      <jats:italic>GSK3\u03b2<\/jats:italic>\n                      , mitochondrial transport, and synaptic plasticity, providing a mechanistic framework for developing AD therapeutics.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71108","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T08:33:07Z","timestamp":1770107587000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Single\u2010cell analysis reveals neuroprotective histone deacetylase inhibitor pathways"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3921-5663","authenticated-orcid":false,"given":"Madeline","family":"Peyton","sequence":"first","affiliation":[{"name":"Department of Biostatistics and Health Data Science Indiana University Indianapolis  Indianapolis Indiana USA"},{"name":"Center for Biomedical Informatics Regenstrief Institute Indianapolis Indiana USA"},{"name":"Indiana Biosciences Research Institute  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur","family":"Jury\u2010Garfe","sequence":"additional","affiliation":[{"name":"Department of Anatomy Cell Biology &amp; Physiology, Indiana University Indianapolis  Indianapolis Indiana USA"},{"name":"Department of Neurology Baylor College of Medicine Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Health Data Science Indiana University Indianapolis  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb","family":"Beimfohr","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Clinical Pharmacology School of Medicine Indiana University Indianapolis  Indianapolis Indiana 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