{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:35:11Z","timestamp":1791815711804,"version":"4.3.4"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T00:00:00Z","timestamp":1590624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002565","name":"Alzheimer's Drug Discovery Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002565","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Preclinical evidence with nilotinib, a US Food and Drug Administration (FDA)\u2010approved drug for leukemia, indicates improvement in Alzheimer's disease phenotypes. We investigated whether nilotinib is safe, and detectable in cerebrospinal fluid, and alters biomarkers and clinical decline in Alzheimer's disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This single\u2010center, phase 2, randomized, double\u2010blind, placebo\u2010controlled study investigated the safety, tolerability, and pharmacokinetics of nilotinib, and measured biomarkers in participants with mild to moderate dementia due to Alzheimer's disease. The diagnosis was supported by cerebrospinal fluid or amyloid positron emission tomography biomarkers. Nilotinib 150 mg versus matching placebo was taken orally once daily for 26\u2009weeks followed by nilotinib 300 mg versus placebo for another 26\u2009weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of the 37 individuals enrolled, 27 were women and the mean (SD) age was 70.7 (6.48) years. Nilotinib was well\u2010tolerated, although more adverse events, particularly mood swings, were noted with the 300 mg dose. In the nilotinib group, central nervous system (CNS) amyloid burden was significantly reduced in the frontal lobe compared to the placebo group. Cerebrospinal fluid A\u03b240 was reduced at 6 months and A\u03b242 was reduced at 12 months in the nilotinib group compared to the placebo. Hippocampal volume loss was attenuated (\u221227%) at 12 months and phospho\u2010tau\u2010181 was reduced at 6 months and 12 months in the nilotinib group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      Nilotinib is safe and achieves pharmacologically relevant cerebrospinal fluid concentrations. Biomarkers of disease were altered in response to nilotinib treatment. These data support a larger, longer, multicenter study to determine the safety and efficacy of nilotinib in Alzheimer's disease. ANN NEUROL 2020\n                      <jats:bold>ANN NEUROL 2020;88:183\u2013194<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.25775","type":"journal-article","created":{"date-parts":[[2020,5,29]],"date-time":"2020-05-29T00:11:21Z","timestamp":1590711081000},"page":"183-194","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":126,"title":["Nilotinib Effects on Safety, Tolerability, and Biomarkers in Alzheimer's Disease"],"prefix":"10.1002","volume":"88","author":[{"given":"Raymond S.","family":"Turner","sequence":"first","affiliation":[{"name":"Memory Disorders Program, Department of Neurology Georgetown University Medical Center  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaeline L.","family":"Hebron","sequence":"additional","affiliation":[{"name":"Translational Neurotherapeutics Program, Laboratory for Dementia and Parkinsonism, Department of Neurology Georgetown University Medical Center  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Lawler","sequence":"additional","affiliation":[{"name":"Movement Disorders Clinic, Department of Neurology MedStar Georgetown University Hospital  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth E.","family":"Mundel","sequence":"additional","affiliation":[{"name":"Movement Disorders Clinic, Department of Neurology MedStar Georgetown University Hospital  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Yusuf","sequence":"additional","affiliation":[{"name":"Movement Disorders Clinic, Department of Neurology MedStar Georgetown University Hospital  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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