{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T01:47:16Z","timestamp":1787881636559,"version":"build-2784847793"},"reference-count":56,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,1,10]],"date-time":"2021-01-10T00:00:00Z","timestamp":1610236800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100014387","name":"ACADIA Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014387","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Amyloid\u2010\u03b2 (A\u03b2) peptide aggregation into soluble oligomers and insoluble plaques is a precipitating event in the pathogenesis of Alzheimer's disease (AD). Given that synaptic activity can regulate A\u03b2 generation, we postulated that 5HT<jats:sub>2A<\/jats:sub>\u2010Rs may regulate A\u03b2 as well. We treated APP\/PS1 transgenic mice with the selective 5HT<jats:sub>2A<\/jats:sub> inverse agonists M100907 or Pimavanserin systemically and measured brain interstitial fluid (ISF) A\u03b2 levels in real\u2010time using in vivo microdialysis. Both compounds reduced ISF A\u03b2 levels by almost 50% within hours, but had no effect on A\u03b2 levels in 5HT<jats:sub>2A<\/jats:sub>\u2010R knock\u2010out mice. The A\u03b2\u2010lowering effects of Pimavanserin were blocked by extracellular\u2010regulated kinase (ERK) and NMDA receptor inhibitors. Chronic administration of Pimavanserin by subcutaneous osmotic pump to aged APP\/PS1 mice significantly reduced CSF A\u03b2 levels and A\u03b2 pathology and improved cognitive function in these mice. Pimavanserin is FDA\u2010approved to treat Parkinson's disease psychosis, and also has been shown to reduce psychosis in a variety of other dementia subtypes including Alzheimer's disease. These data demonstrate that Pimavanserin may have disease\u2010modifying benefits in addition to its efficacy against neuropsychiatric symptoms of Alzheimer's disease.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15260-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>Read the Editorial Highlight for this article on page <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/doi.org\/10.1111\/jnc.15269\">560<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.15260","type":"journal-article","created":{"date-parts":[[2020,12,5]],"date-time":"2020-12-05T16:46:46Z","timestamp":1607186806000},"page":"658-673","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Pimavanserin, a 5HT<sub>2A<\/sub> receptor inverse agonist, rapidly suppresses A\u03b2 production and related pathology in a mouse model of Alzheimer\u2019s disease"],"prefix":"10.1111","volume":"156","author":[{"given":"Carla M.","family":"Yuede","sequence":"first","affiliation":[{"name":"Department of Neurology Washington University School of Medicine St. Louis MO USA"},{"name":"Knight Alzheimer\u2019s Disease Research Center Washington University School of Medicine St. Louis MO USA"},{"name":"Hope Center for Neurological Disorders Washington University School of Medicine St. Louis MO 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