{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T15:54:13Z","timestamp":1770134053105,"version":"3.49.0"},"reference-count":22,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["1U01AG066722"],"award-info":[{"award-number":["1U01AG066722"]}]},{"name":"NIH","award":["9942787"],"award-info":[{"award-number":["9942787"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Alzheimer\u2019s disease (AD) is a multifactorial neurodegenerative disorder and the leading cause of dementia worldwide. Progressive synaptic dysfunction underlies declines in cognition, daily functioning, and the development of neuropsychiatric syndromes. Neuropsychiatric syndromes that include agitation and aggression affect 40\u201360% of patients and represent a major source of caregiver burden. Serotonin 5-HT2B receptor levels are increased in the AD patient brain, and thus, treatment of AD animal models with the selective 5-HT2B receptor antagonist MW073 in prevention or disease stage paradigms attenuates A\u03b2- or tau-induced dysfunction. Methods: We investigated the effects of MW073 treatment on the aggressive behavior of Tg2576 mice in a resident\u2013intruder assay. Results: MW073 treatment significantly reduced aggressive behavior in male Tg2576 mice. Conclusions: MW073 efficacy in treating aggression in Tg2576 mice implicates 5-HT2B receptor-mediated signaling in AD neuropsychiatric symptoms as well as cognitive and behavioral dysfunction.<\/jats:p>","DOI":"10.3390\/cells15030273","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T12:49:44Z","timestamp":1770036584000},"page":"273","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Highly Selective 5-HT2B Receptor Antagonist MW073 Mitigates Aggressive Behavior in an Alzheimer\u2019s Disease Mouse Model"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3266-8115","authenticated-orcid":false,"given":"Erica","family":"Acquarone","sequence":"first","affiliation":[{"name":"Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, 630 West 168th Street, P&S 12-420D, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9096-0491","authenticated-orcid":false,"given":"Saktimayee M.","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Feinberg School of Medicine, Northwestern University, 320 E. Superior St., Chicago, IL 60611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2362-9587","authenticated-orcid":false,"given":"Agnieszka","family":"Staniszewski","sequence":"additional","affiliation":[{"name":"Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, 630 West 168th Street, P&S 12-420D, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7605-5866","authenticated-orcid":false,"given":"Daniel Martin","family":"Watterson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Feinberg School of Medicine, Northwestern University, 320 E. Superior St., Chicago, IL 60611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6335-164X","authenticated-orcid":false,"given":"Ottavio","family":"Arancio","sequence":"additional","affiliation":[{"name":"Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, 630 West 168th Street, P&S 12-420D, New York, NY 10032, USA"},{"name":"Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA"},{"name":"Department of Medicine, Columbia University, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41582-021-00591-9","article-title":"Disease Modification Is Not All\u2014We Need Symptomatic Therapies for Alzheimer Disease","volume":"18","author":"Cummings","year":"2022","journal-title":"Nat. Rev. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.jagp.2024.01.024","article-title":"The Neuropathological Underpinnings of Neuropsychiatric Symptoms in Dementia","volume":"32","author":"Sachdev","year":"2024","journal-title":"Am. J. Geriatr. Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1002\/gps.5030","article-title":"Using Electronic Health Records to Estimate the Prevalence of Agitation in Alzheimer Disease\/Dementia","volume":"34","author":"Halpern","year":"2019","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1002\/gps.5604","article-title":"Impact of Agitation in Long-term Care Residents with Dementia in the United States","volume":"36","author":"Fillit","year":"2021","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.3233\/JAD-200127","article-title":"Real-World Treatment Patterns and Characteristics Among Patients with Agitation and Dementia in the United States: Findings from a Large, Observational, Retrospective Chart Review","volume":"77","author":"Aigbogun","year":"2020","journal-title":"J. Alzheimer\u2019s Dis. JAD"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1007\/s40265-025-02227-4","article-title":"Current and Emerging Pharmacological Approaches to Agitation in Alzheimer\u2019s Disease: A Narrative Review of New and Repurposed Therapies","volume":"85","author":"Smoller","year":"2025","journal-title":"Drugs"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1007\/s40263-025-01219-y","article-title":"Brexpiprazole for the Treatment of Agitation in Older Adults with Alzheimer\u2019s Disease: A Systematic Review, Bayesian Meta-Analysis, and Meta-Regression","volume":"39","author":"Cal","year":"2025","journal-title":"CNS Drugs"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1111\/j.1365-2990.2008.00997.x","article-title":"Brazilian Brain Bank Study Group. The Dorsal Raphe Nucleus Shows Phospho-Tau Neurofibrillary Changes before the Transentorhinal Region in Alzheimer\u2019s Disease. A Precocious Onset?","volume":"35","author":"Grinberg","year":"2009","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.nbd.2017.05.007","article-title":"Molecular Imaging of Serotonin Degeneration in Mild Cognitive Impairment","volume":"105","author":"Smith","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1046\/j.0305-1846.2000.00291.x","article-title":"The Evolution of Alzheimer\u2019s Disease-related Cytoskeletal Pathology in the Human Raphe Nuclei","volume":"26","author":"Schultz","year":"2000","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1097\/NEN.0b013e318232a379","article-title":"Stages of the Pathologic Process in Alzheimer Disease: Age Categories from 1 to 100 Years","volume":"70","author":"Braak","year":"2011","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.3233\/JAD-240063","article-title":"The 5HT2b Receptor in Alzheimer\u2019s Disease: Increased Levels in Patient Brains and Antagonist Attenuation of Amyloid and Tau Induced Dysfunction","volume":"98","author":"Acquarone","year":"2024","journal-title":"J. Alzheimer\u2019s Dis. JAD"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"23582","DOI":"10.1038\/s41598-021-02900-0","article-title":"Evaluation of a 5-HT2B Receptor Agonist in a Murine Model of Amyotrophic Lateral Sclerosis","volume":"11","author":"Arnoux","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"17415","DOI":"10.18632\/oncotarget.8277","article-title":"Up-Regulation of Serotonin Receptor 2B mRNA and Protein in the Peri-Infarcted Area of Aged Rats and Stroke Patients","volume":"7","author":"Buga","year":"2016","journal-title":"Oncotarget"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/nature09629","article-title":"A Population-Specific HTR2B Stop Codon Predisposes to Severe Impulsivity","volume":"468","author":"Bevilacqua","year":"2010","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e70073","DOI":"10.1002\/trc2.70073","article-title":"Optimized 5-HT2b Inhibitors for Neuropsychiatric Syndromes with Cognitive Dysfunction","volume":"11","author":"Roy","year":"2025","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1038\/s41598-018-37613-4","article-title":"Brain Serotonin Deficiency Affects Female Aggression","volume":"9","author":"Richter","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/7854_2011_191","article-title":"Behavioral and Pharmacogenetics of Aggressive Behavior","volume":"12","author":"Takahashi","year":"2012","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s00213-012-2654-8","article-title":"Behavioral Characterization of Escalated Aggression Induced by GABA(B) Receptor Activation in the Dorsal Raphe Nucleus","volume":"224","author":"Takahashi","year":"2012","journal-title":"Psychopharmacology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/7854_2013_263","article-title":"Neurogenetics of Aggressive Behavior: Studies in Rodents","volume":"17","author":"Takahashi","year":"2014","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1196\/annals.1330.022","article-title":"Serotonin and Aggression","volume":"1036","author":"Olivier","year":"2004","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1007\/s00213-002-1139-6","article-title":"Social and Neural Determinants of Aggressive Behavior: Pharmacotherapeutic Targets at Serotonin, Dopamine and Gamma-Aminobutyric Acid Systems","volume":"163","author":"Miczek","year":"2002","journal-title":"Psychopharmacology"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/3\/273\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T05:14:36Z","timestamp":1770095676000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/3\/273"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,1]]},"references-count":22,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["cells15030273"],"URL":"https:\/\/doi.org\/10.3390\/cells15030273","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,1]]}}}