{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:42:07Z","timestamp":1792554127912,"version":"4.5.0"},"reference-count":46,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171198"],"award-info":[{"award-number":["82171198"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Plasma phosphorylated tau (p\u2010tau)217 is increasingly used to triage amyloid testing, but the biological and clinical meaning of discordant plasma p\u2010tau217 and amyloid positron emission tomography (PET) results in cognitively normal adults remains uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We analyzed cognitively normal participants from the Chinese Preclinical Alzheimer's Disease Study (CPAS;\n                      <jats:italic>n\u00a0=<\/jats:italic>\n                      \u00a0594) and the Alzheimer's Disease Neuroimaging Initiative (ADNI;\n                      <jats:italic>n\u00a0=<\/jats:italic>\n                      \u00a0475). Amyloid PET positivity was defined as Centiloid \u2265 20. Cohort\u2010specific p\u2010tau217 positivity was defined using PET\u2010anchored cutoffs with \u2265 0.90 specificity, yielding four p\u2010tau\/PET groups. Linear models assessed cross\u2010sectional biomarker and cognitive differences; mixed\u2010effects and Cox models assessed ADNI longitudinal Centiloid accumulation, cognitive trajectories, and clinical progression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>In cross\u2010sectional analyses, compared to p\u2010tau\u2212\/PET\u2212, p\u2010tau+\/PET\u2212 had higher glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) levels across cohorts; p\u2010tau\u2212\/PET+ showed a lower plasma amyloid beta 42\/40 ratio in ADNI; and p\u2010tau+\/PET+ showed the broadest multimodal abnormalities. In ADNI, both p\u2010tau+ groups had higher clinical progression risk and faster decline in selected cognitive domains; both PET+ groups showed faster Centiloid accumulation. Faster Centiloid accumulation in p\u2010tau+\/PET\u2212 was observed only at lower specificity thresholds.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Discordant plasma p\u2010tau217 and amyloid PET results should be interpreted according to both the positivity pattern and the p\u2010tau217 cutoff applied. Distinguishing these patterns may aid risk stratification and longitudinal monitoring. Different p\u2010tau217 operating points may support risk enrichment and prioritization for confirmatory amyloid testing, but require validation before clinical use.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71922","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:14:51Z","timestamp":1792552491000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Direction\u2010specific biomarker profiles and clinical significance of plasma p\u2010tau217\/amyloid PET discordance in cognitively normal adults"],"prefix":"10.1002","volume":"22","author":[{"given":"Yanlu","family":"Huang","sequence":"first","affiliation":[{"name":"Health Management Center Shenzhen Qianhai Taikang Hospital  Shenzhen China"},{"name":"Department of Gerontology Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai 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