{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:58:39Z","timestamp":1759971519774,"version":"build-2065373602"},"reference-count":44,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T00:00:00Z","timestamp":1727222400000},"content-version":"vor","delay-in-days":0,"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":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Small molecules and antibodies are being developed to lower amyloid beta (A\u03b2) peptides.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We describe MEDI1814, a fully human high\u2010affinity monoclonal antibody selective for A\u03b2<jats:sub>42<\/jats:sub>, the pathogenic self\u2010aggregating species of A\u03b2.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>MEDI1814 reduces free A\u03b2<jats:sub>42<\/jats:sub> without impacting A\u03b2<jats:sub>40<\/jats:sub> in the cerebrospinal fluid of rats and cynomolgus monkeys after systemic administration. MEDI1814 administration to patients with Alzheimer's disease (AD; <jats:italic>n<\/jats:italic>\u00a0=\u00a057) in single or repeat doses up to 1800\u00a0mg intravenously or 200\u00a0mg subcutaneously was associated with a favorable safety and tolerability profile. No cases of amyloid\u2010related imaging abnormalities were observed. Predictable dose\u2010proportional changes in serum exposures for MEDI1814 were observed across cohorts. Cerebrospinal fluid (CSF) analysis demonstrated central nervous system penetration of MEDI1814. Pharmacodynamic data showed dose\u2010dependent suppression of free A\u03b2<jats:sub>42<\/jats:sub>, increases in total (bound and free) A\u03b2<jats:sub>42<\/jats:sub>, but no change in total A\u03b2<jats:sub>40<\/jats:sub> in CSF across doses.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>MEDI1814 offers a differentiated approach to impacting A\u03b2 in AD via selective reduction of free A\u03b2<jats:sub>42<\/jats:sub>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14238","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T11:44:16Z","timestamp":1727264656000},"page":"7762-7776","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MEDI1814 selectively reduces free A\u03b242 in cerebrospinal fluid of non\u2010clinical species and Alzheimer's disease 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