{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T07:16:45Z","timestamp":1783322205686,"version":"3.54.6"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>S\u2010adenosyl methionine (SAMe) is a pivotal metabolite in multiple neuronal pathways, including tau dephosphorylation. Reduced SAMe availability has been reported in the Alzheimer's disease (AD) brain, prompting interest in supplementation as a potential therapeutic strategy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      This multicenter, randomized, double\u2010blind, placebo\u2010controlled phase 2 study recruited people (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a063) with a clinical AD diagnosis. Participants received 180 days of SAMe (400\u00a0mg daily) or placebo. Primary outcome was change in plasma phosphorylated tau (p\u2010tau)217 concentration. Secondary endpoints included safety, tolerability, and cognitive outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Mean percentage change in plasma p\u2010tau217 in the SAMe group was an increase of 53.22 (standard deviation [SD] 159.19) compared to 25.34 (SD 94.83) in the placebo group (standardized mean difference 37.58, 95% confidence interval \u221232.61, 107.76;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.288). No significant differences were observed in safety or other secondary endpoints.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>SAMe did not demonstrate disease\u2010modifying efficacy at the dose and duration studied; however it was safe and well tolerated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>\n                      ACTRN12620000506998. Registered on the Australian New Zealand Clinical Trials Registry (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.anzctr.org.au\">http:\/\/www.anzctr.org.au<\/jats:ext-link>\n                      )\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71381","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T02:58:31Z","timestamp":1776221911000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A phase 2, randomized, multicenter, double\u2010blind, placebo\u2010controlled trial of S\u2010adenosyl methionine in participants with mild cognitive impairment or dementia due to Alzheimer's disease"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4257-964X","authenticated-orcid":false,"given":"Sarah","family":"Holper","sequence":"first","affiliation":[{"name":"Department of Medicine, Melbourne Brain Centre, The Royal Melbourne Hospital University of Melbourne  Parkville Victoria Australia"},{"name":"Genetics and Gene Regulation, The Walter and Eliza Hall Institute of Medical Research  Parkville Victoria Australia"},{"name":"National Dementia Diagnostics Laboratory The Florey Institute of Neuroscience and Mental Health  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J.","family":"Barnham","sequence":"additional","affiliation":[{"name":"National Dementia Diagnostics Laboratory The Florey Institute of Neuroscience and Mental Health  Parkville Victoria 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