{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:28:07Z","timestamp":1792096087808,"version":"4.4.0"},"reference-count":75,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T00:00:00Z","timestamp":1767484800000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["AARG\u201022\u2010973496"],"award-info":[{"award-number":["AARG\u201022\u2010973496"]}],"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":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Amyloid\u2010induced tauopathy drives clinical decline in Alzheimer's disease (AD). Because age and sex shape tau trajectories, defining patient\u2010centered amyloid thresholds for tauopathy onset could facilitate pre\u2010tauopathy AD identification and aid treatment decisions and prognosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      By including two samples (Alzheimer's Disease Neuroimaging Initiative [ADNI,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0301]; and 18F\u2010AV\u20101451\u2010A05 [A05,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0143]), we explored whether age and sex affect tauopathy transition and determined patient\u2010centered amyloid positron emission tomography (PET) thresholds that mark tauopathy onset.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      We found a consistent amyloid PET \u00d7 age interaction on global tau PET increase in men (ADNI\/A05:\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.0078\/0.018), with younger men showing faster amyloid\u2010associated tau accumulation. We then established patient\u2010centered, amyloid PET\u2013inferred tauopathy transition cut\u2010offs. Women reached this transition at lower amyloid PET levels, and these cutoffs predicted both earlier onset and accelerated cognitive decline (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>This study highlights the effect of age and sex on the amyloid\u2010to\u2010tauopathy transition, establishes patient\u2010centered amyloid PET thresholds for tauopathy onset, and links these thresholds to accelerated cognitive decline.<\/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>Younger age is related to faster amyloid\u2010related tau accumulation in men.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We defined a series of amyloid positron emission tomography (PET) thresholds to enable patient\u2010centered inference of amyloid\u2010related tauopathy.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Crossing the amyloid PET\u2013defined tauopathy phase is associated with more progressive tau deposition and cognitive decline.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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