{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:53:47Z","timestamp":1777395227628,"version":"3.51.4"},"reference-count":46,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T00:00:00Z","timestamp":1614211200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2021,4,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Whether the epidemiological association of amyloid-\u03b2 (A\u03b2) and tau pathology in late-onset Alzheimer\u2019s disease (LOAD) is causal remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>We aimed to investigate the shared genetic background between the cerebrospinal fluid (CSF) biomarkers for A\u03b2 and tau pathology and the risk of LOAD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We conducted a two-sample Mendelian randomization (MR) analysis. We used summary statistics of genome-wide association studies for CSF biomarkers (A\u03b2\n                      <jats:sub>1\u201342<\/jats:sub>\n                      [A\u03b2], phosphorylated tau\n                      <jats:sub>181<\/jats:sub>\n                      [p-tau], and total tau [t-tau]) in 3,146 individuals and for LOAD in 21,982 cases and 41,944 controls. We tested the association between changes in the genetically predicted CSF biomarkers and LOAD risk.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      We found a decrease in LOAD risk per one-standard-deviation (SD) increase in the genetically predicted CSF A\u03b2 (odds ratio [OR], 2.87\u00d710\n                      <jats:sup>\u20133<\/jats:sup>\n                      for AD; 95%confidence interval [CI], 1.54\u00d710\n                      <jats:sup>\u20134<\/jats:sup>\n                      \u20130.05; p\u200a=\u200a8.91\u00d710\n                      <jats:sup>\u20135<\/jats:sup>\n                      ). Conversely, we observed an increase in LOAD risk per one-SD increase in the genetically predicted CSF p-tau (OR, 19.46; 95%CI, 1.50\u20132.52\u00d710\n                      <jats:sup>2<\/jats:sup>\n                      ; p\u200a=\u200a0.02) and t-tau (OR, 33.80; 95%CI, 1.57\u20137.29\u00d710\n                      <jats:sup>2<\/jats:sup>\n                      ; p\u200a=\u200a0.02). However, only the association between p-tau and the risk for LOAD remained significant after the exclusion of the APOE variant (rs769449).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>We found the causal association between CSF biomarkers and the risk for LOAD. Our results suggest that the etiology of LOAD involves multiple biological processes, including the pathways of A\u03b2 and tau proteins. Further MR studies using large-scale data of multiple candidate biomarkers are needed to elucidate the pathophysiology of LOAD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-200671","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T12:11:07Z","timestamp":1614341467000},"page":"1197-1207","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Shared Genetic Background Between Cerebrospinal Fluid Biomarkers and Risk for Alzheimer\u2019s Disease: A Two-Sample Mendelian Randomization Study"],"prefix":"10.1177","volume":"80","author":[{"given":"Soyeon","family":"Kim","sequence":"first","affiliation":[{"name":"Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Samsung Medical Center, Seoul, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiwon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Veteran Health Service Medical Center, Seoul, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwangsik","family":"Nho","sequence":"additional","affiliation":[{"name":"Department of Radiology & Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woojae","family":"Myung","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong-Hee","family":"Won","sequence":"additional","affiliation":[{"name":"Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Samsung Medical Center, Seoul, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2021,2,25]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2007.04.381"},{"key":"ref002","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.12050"},{"key":"ref003","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182840bbe"},{"issue":"1","key":"ref004","first-page":"S87","volume":"33","author":"Sagare AP","year":"2013","journal-title":"J Alzheimers Dis"},{"key":"ref005","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0289-8"},{"key":"ref006","doi-asserted-by":"publisher","DOI":"10.1097\/00006842-200205000-00014"},{"key":"ref007","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu328"},{"key":"ref008","doi-asserted-by":"publisher","DOI":"10.1007\/s40471-017-0128-6"},{"key":"ref009","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1685-y"},{"key":"ref010","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0358-2"},{"key":"ref011","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21610"},{"key":"ref012","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.02.026"},{"key":"ref013","doi-asserted-by":"publisher","DOI":"10.1038\/srep18092"},{"key":"ref014","doi-asserted-by":"publisher","DOI":"10.1177\/0962280215597579"},{"key":"ref015","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0350-x"},{"key":"ref016","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408"},{"key":"ref017","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21998"},{"key":"ref018","doi-asserted-by":"publisher","DOI":"10.1097\/JGP.0b013e318259b9a5"},{"key":"ref019","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2012.263"},{"key":"ref020","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2017.78"},{"key":"ref021","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-25460-2"},{"key":"ref022","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.j5375"},{"key":"ref023","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001841"},{"key":"ref024","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000010463"},{"key":"ref025","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21965"},{"key":"ref026","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyx102"},{"key":"ref027","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyu005"},{"key":"ref028","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01261-5"},{"key":"ref029","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080"},{"key":"ref030","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)00070-3"},{"key":"ref031","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2028-17.2017"},{"key":"ref032","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-015-1390-7"},{"key":"ref033","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1706441"},{"key":"ref034","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002660"},{"key":"ref035","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-141959"},{"key":"ref036","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31275-2"},{"key":"ref037","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5284.99"},{"key":"ref038","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01879.x"},{"key":"ref039","doi-asserted-by":"publisher","DOI":"10.1126\/science.1242077"},{"key":"ref040","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-018-0013-z"},{"key":"ref041","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008864"},{"key":"ref042","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0173(00)00019-9"},{"key":"ref043","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21041505"},{"key":"ref044","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0063644"},{"key":"ref045","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-018-0246-7"},{"key":"ref046","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-020-00683-8"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-200671","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3233\/JAD-200671","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-200671","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:05:13Z","timestamp":1777370713000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JAD-200671"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,25]]},"references-count":46,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,4,6]]}},"alternative-id":["10.3233\/JAD-200671"],"URL":"https:\/\/doi.org\/10.3233\/jad-200671","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/719898","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-17511\/v1","asserted-by":"object"}]},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,25]]}}}