{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:02:06Z","timestamp":1790402526484,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":75,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100010302","name":"Robert A. and Renee E. Belfer Family Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010302","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;D Transl Res &amp; Clin Interv"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>\n                      With the advent of early detection biomarkers, it is possible to envision testing preventive strategies that delay the onset of Alzheimer's disease (AD). The \u03b54 allele of apolipoprotein E (\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54) is the strongest genetic risk factor for late\u2010onset AD; approximately 50% of all patients are\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54\u2010positive.\n                      <jats:sup>1<\/jats:sup>\n                      APOE is the major central nervous system (CNS) lipoprotein, and studies have linked APOE4\u2010dependent deficits in lipid metabolism to disease\u2010relevant processes.\n                      <jats:sup>2\u20136<\/jats:sup>\n                      Choline, the precursor for phosphatidylcholine (PC), normalizes\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54\u2010mediated lipid dysfunction in human model systems,\n                      <jats:sup>6<\/jats:sup>\n                      and low dietary choline intake correlates with increased disease risk or progression in mouse models and humans.\n                      <jats:sup>7\u201317<\/jats:sup>\n                      We therefore tested whether biomarkers and omics provided early evidence of choline CNS target engagement in an at\u2010risk population.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      In a 6\u2010month open\u2010label phase 1 study (NCT05880849), asymptomatic\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 carriers (\n                      <jats:italic>n =<\/jats:italic>\n                      13; age 70 \u00b1 5.5 years) received 2200\u00a0mg\/day oral choline, with plasma and cerebrospinal fluid (CSF) collected before and after treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Choline was well tolerated with no serious adverse events. Treatment increased plasma and CSF choline and betaine, indicating systemic and CNS exposure. Exploratory lipidomics identified changes in plasma PC species and, in CSF, increases in ceramides and cholesterol esters. Although this study was not powered to assess biomarker efficacy, CSF neurofilament light (NfL) was lower at the end of treatment, and CSF phosphoserine\u2010181 tau (pTau181)\/amyloid beta (A\u03b2)42 and plasma pTau217 showed directionally similar trends.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These findings support randomized placebo\u2010controlled trials of choline in at\u2010risk populations and illustrate how fluid biomarkers and omics can de\u2010risk AD prevention studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.70323","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:06:08Z","timestamp":1789448768000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of choline supplementation in presymptomatic\n                    <i>APOE \u03b54<\/i>\n                    carriers: a pilot study"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4491-167X","authenticated-orcid":false,"given":"William J.","family":"Ray","sequence":"first","affiliation":[{"name":"Belfer Neurodegeneration Consortium, Therapeutics Discovery Division University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaima L.","family":"Lightfoot","sequence":"additional","affiliation":[{"name":"Belfer Neurodegeneration Consortium, Therapeutics Discovery Division University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronnie T.","family":"Trinh","sequence":"additional","affiliation":[{"name":"Belfer Neurodegeneration Consortium, Therapeutics Discovery Division University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janelle","family":"Fawver\u2010Kahle","sequence":"additional","affiliation":[{"name":"Belfer Neurodegeneration Consortium, Therapeutics Discovery Division University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Cooper","sequence":"additional","affiliation":[{"name":"Neurocognitive Disorders Center McGovern Medical School at UTHealth Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Huei","family":"Tsai","sequence":"additional","affiliation":[{"name":"Picower Institute for Learning and Memory Department of Brain and Cognitive Sciences Massachusetts Institute of Technology  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Bortz","sequence":"additional","affiliation":[{"name":"Balchem Corporation  Montvale New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isis","family":"Trujillo\u2010Gonzalez","sequence":"additional","affiliation":[{"name":"Nutrition Research Institute University of North Carolina at Chapel Hill  Kannapolis North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics &amp; Data Science School of Public Health UTHealth Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hulin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics &amp; Data Science School of Public Health UTHealth Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guadalupe J. 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