{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T19:38:35Z","timestamp":1774381115378,"version":"3.50.1"},"reference-count":96,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Amyloid precursor protein (APP) undergoes striking changes following traumatic brain injury (TBI). Considering its role in the control of gene expression, we investigated whether APP regulates transcription and translation following TBI.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We assessed brain morphology (<jats:italic>n<\/jats:italic>\u00a0=\u00a04\u20139 mice\/group), transcriptome (<jats:italic>n<\/jats:italic>\u00a0=\u00a03 mice\/group), proteome (<jats:italic>n<\/jats:italic>\u00a0=\u00a03 mice\/group), and behavior (<jats:italic>n<\/jats:italic>\u00a0=\u00a017\u201327 mice\/group) of wild\u2010type (WT) and APP knock\u2010out (KO) mice either untreated or 10\u2010weeks following TBI.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>After TBI, WT mice displayed transcriptional programs consistent with late stages of brain repair, hub genes were predicted to impact translation and brain proteome showed subtle changes. APP KO mice largely replicated this transcriptional repertoire, but showed no transcriptional nor translational response to TBI.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>The similarities between WT mice following TBI and APP KO mice suggest that developmental APP deficiency induces a condition reminiscent of late stages of brain repair, hampering the control of gene expression in response to injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>10\u2010weeks after TBI, brains exhibit transcriptional profiles consistent with late stage of brain repair.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Developmental APP deficiency maintains brains perpetually in an immature state akin to late stages of brain repair.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>APP responds to TBI by changes in gene expression at a transcriptional and translational level.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>APP deficiency precludes molecular brain changes in response to TBI.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.70093","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T06:11:18Z","timestamp":1745475078000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Developmental deletion of amyloid precursor protein precludes transcriptional and proteomic responses to brain injury"],"prefix":"10.1002","volume":"21","author":[{"given":"Valentina","family":"Lacovich","sequence":"first","affiliation":[{"name":"Translational Aging and Neuroscience Program Center for Translational Medicine International Clinical Research Center St. Anne's University Hospital  Brno Czech Republic"},{"name":"Central European Institute of Technology at Masaryk University (CEITEC MU)  Brno Czech 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