{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:03:36Z","timestamp":1790334216944,"version":"4.1.0"},"reference-count":82,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["22\u2010AAIIA\u2010953269"],"award-info":[{"award-number":["22\u2010AAIIA\u2010953269"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Late\u2010onset Alzheimer's disease (LOAD) and major depressive disorder (MDD) share genetic etiologies. Here, we investigated brain transcriptomic landscapes to gain insights into shared and divergent molecular and biological etiologies across LOAD and MDD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Brain single\u2010nucleus RNA sequencing (snRNA\u2010seq) datasets from cognitively normal older and young individuals and LOAD patients stratified by comorbid MDD were analyzed to identify differential expressed genes (DEGs). Using cell type\u2013specific DEGs we performed biological pathway and intercellular\u2010communication networks analyses. We investigated shared DEGs across MDD and LOAD cohorts and sex\u2010specific DEGs. Results were validated by comparison with four transcriptomic and proteomic studies of MDD and depression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      MDD\u2010associated dysregulated genes and pathways were shared between LOAD and cognitive\u2010normal individuals, including\n                      <jats:italic>JUNB<\/jats:italic>\n                      and\n                      <jats:italic>DUSP1<\/jats:italic>\n                      in glutamatergic neurons, and\n                      <jats:italic>PRAM1<\/jats:italic>\n                      and\n                      <jats:italic>SNX9<\/jats:italic>\n                      in microglia. DEGs shared between the MDD and LOAD cohorts included\n                      <jats:italic>HSPA1A<\/jats:italic>\n                      and\n                      <jats:italic>NDUFB7<\/jats:italic>\n                      in glutamatergic neurons. Sex interaction analysis identified numerous new DEGs in the MDD cohorts, whereas there were \u22485 to 10 times more DEGs in female than in male individuals. LOAD and MDD common microglial pathways included neuronal injury, stress, peroxisome proliferator\u2010activated receptor (PPAR) signaling and interferon alpha\/beta signaling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>LOAD and MDD exhibited common molecular profiles, dysregulated pathways, and cellular communication changes. MDD develops earlier in life, thus, our findings provide a window into early molecular and biological processes preceding LOAD\u2010onset.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71823","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T05:23:53Z","timestamp":1789190633000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cellular transcriptomic signatures underpinning the heterogeneity of depression in Alzheimer's disease"],"prefix":"10.1002","volume":"22","author":[{"given":"Michael W.","family":"Lutz","sequence":"first","affiliation":[{"name":"Division of Translational Brain Sciences, Department of Neurology Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui","family":"Man","sequence":"additional","affiliation":[{"name":"Division of Translational Brain Sciences, Department 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