{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:19:57Z","timestamp":1790864397351,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102023\u201000262527"],"award-info":[{"award-number":["RS\u20102023\u201000262527"]}],"id":[{"id":"10.13039\/501100003725","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":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Polygenic risk score (PRS) identifies individuals at high genetic risk for Alzheimer's disease (AD), but its utility in predicting cognitive trajectories and AD pathologies remains unclear. We optimized PRS (optPRS) for AD, investigated its association with cognitive trajectories and AD phenotypes of cerebral organoids.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Using genome\u2010wide association study (GWAS) summary statistics from a European population, we developed optPRS to predict AD in Korean individuals (n\u00a0=\u00a01634). We analyzed the association between optPRS and cognitive trajectories (n\u00a0=\u00a0771). We generated induced pluripotent stem cell\u2013derived cerebral organoids from patients with high (n\u00a0=\u00a03) and low (n\u00a0=\u00a04) optPRS to evaluate amyloid beta (A\u03b2) and phosphorylated tau (p\u2010tau) levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      OptPRS predicted AD dementia and A\u03b2 positivity, independent of apolipoprotein E (\n                      <jats:italic>APOE<\/jats:italic>\n                      ). Higher optPRSs correlated with rapid cognitive decline. Cerebral organoids from the high optPRS group exhibited increased A\u03b2 insolubility and p\u2010tau levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>OptPRS predicted cognitive decline and AD phenotypes of cerebral organoids, supporting its use in risk assessments and drug\u2010screening platform.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Optimized polygenic risk scores (optPRSs) improve the prediction of Alzheimer's disease (AD) dementia and amyloid beta positivity (A\u03b2+).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>High optPRS is associated with faster cognitive decline, particularly in A\u03b2+.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Induced pluripotent stem cell (iPSC)\u2013derived cerebral organoids from high optPRSs show high A\u03b2 insolubility and phosphorylated tau (p\u2010tau).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>PRS genetic risk stratification provides insight into AD progression and pathology.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70660","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T08:55:51Z","timestamp":1758099351000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Polygenic risk score of Alzheimer's disease is associated with cognitive trajectories and phenotypes of cerebral organoids"],"prefix":"10.1002","volume":"21","author":[{"given":"Min Young","family":"Chun","sequence":"first","affiliation":[{"name":"Departments of Neurology, Samsung Medical Center Sungkyunkwan University School of Medicine  Seoul South Korea"},{"name":"Department of Neurology Yonsei University College of Medicine  Seoul South Korea"},{"name":"Department of Neurology, Yongin Severance Hospital Yonsei University Health System  Yongin South 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