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Despite extensive research, effective disease-modifying therapies remain limited, highlighting the need for translationally relevant models and repurposable therapeutic candidates. Dexmedetomidine (DEX), an \u03b12-adrenergic receptor agonist with known neuroprotective properties, was investigated in an adult zebrafish model of AD established through cerebroventricular administration of A\u03b242. DEX treatment significantly reduced A\u03b2 accumulation and was associated with reduced amyloidogenic gene expression, indicating transcriptional changes in amyloidogenic pathway-related genes. DEX attenuated neuroinflammation by reducing glial activation, lowering pro-inflammatory cytokine gene expression, and increasing expression of the anti-inflammatory gene\n                    <jats:italic>il10<\/jats:italic>\n                    . Immunofluorescence assessment further demonstrated reduced astrogliosis and preserved neuronal marker integrity, as indicated by increased HuC\/D levels. Interestingly, DEX attenuated A\u03b2-induced proliferative responses, characterized by decreased PCNA expression, while enhancing cleaved caspase-3 levels, suggesting changes in proliferation and apoptotic signaling under A\u03b2 stress conditions. Behavioral assessments further demonstrated that DEX alleviated A\u03b242-induced anxiety- and aggression-like behaviors, improving behavioral phenotypes in this model. Overall, these findings underscore the multi-level effects of DEX in modulating AD-related pathological features. As a clinically available agent, DEX represents a promising candidate for repurposing in neurodegenerative disease contexts. Further preclinical studies in mammalian models are warranted to validate its translational relevance and therapeutic potential.\n                  <\/jats:p>","DOI":"10.1007\/s12035-026-05906-9","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T02:55:24Z","timestamp":1777949724000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dexmedetomidine Exerts Multi-level Effects to Ameliorate Alzheimer\u2019s Disease Pathology in the Adult Zebrafish Brain"],"prefix":"10.1007","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3888-3377","authenticated-orcid":false,"given":"Dilek","family":"Nazli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4102-3594","authenticated-orcid":false,"given":"Yusuf Kaan","family":"Poyraz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1812-2711","authenticated-orcid":false,"given":"Kubilay","family":"Can","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7369-577X","authenticated-orcid":false,"given":"Dogac","family":"Ipekgil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1299-6784","authenticated-orcid":false,"given":"Nilay","family":"Cakmak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9988-1902","authenticated-orcid":false,"given":"Ebru","family":"Turhanlar-Sahin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7017-1512","authenticated-orcid":false,"given":"Sevcan","family":"Hacoglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4887-1337","authenticated-orcid":false,"given":"Hale Aksu","family":"Erdost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9055-7018","authenticated-orcid":false,"given":"Leyla","family":"Iyilikci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4806-5917","authenticated-orcid":false,"given":"Gunes","family":"Ozhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"issue":"10","key":"5906_CR1","doi-asserted-by":"publisher","first-page":"4388","DOI":"10.1002\/alz.13081","volume":"19","author":"K Dhana","year":"2023","unstructured":"Dhana K, Beck T, Desai P, Wilson RS, Evans DA, Rajan KB (2023) Prevalence of Alzheimer\u2019s disease dementia in the 50 US states and 3142 counties: a population estimate using the 2020 bridged-race postcensal from the National Center for Health Statistics. 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