{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T22:00:29Z","timestamp":1790978429232,"version":"4.1.0"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"ABC-DS","award":["U01AG051406"],"award-info":[{"award-number":["U01AG051406"]}]},{"name":"ABC-DS","award":["U01AG051412"],"award-info":[{"award-number":["U01AG051412"]}]},{"name":"ABC-DS","award":["U19 AG068054-04"],"award-info":[{"award-number":["U19 AG068054-04"]}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Down syndrome is characterized by triplication of chromosome 21, leading to early-onset Alzheimer\u2019s disease pathology, with nearly all individuals with Down syndrome developing amyloid and tau pathology. In the new era of amyloid-modifying therapies, it is vital to identify early biomarkers for Alzheimer\u2019s disease pathology in Down syndrome. Striatal amyloid may begin to accumulate sooner than cortical amyloid in Down syndrome. Tau phosphorylation at specific sites, including 217, can be quantified in plasma and may represent an important mechanistic step in the development of tau pathology. This study had two aims: (i) to compare the relative age at increase of multiple biomarkers (cortical amyloid, striatal amyloid, plasma pTau217 and summary tau pathology); and (ii) to test whether plasma pTau217 can identify both the current presence and likely future accumulation of amyloid and tau pathology.<\/jats:p>\n                  <jats:p>To identify optimal biomarkers for early intervention, we examined longitudinal cortical and striatal amyloid PET, plasma pTau217 and tau PET in 328 individuals with Down syndrome enrolled in the Alzheimer Biomarker Consortium\u2014Down Syndrome study. To compare the timing of biomarker changes, we modelled longitudinal biomarkers using generalized additive mixed models relative to age. We used receiver operating characteristic curve analysis to identify thresholds for both current and likely future accumulation of amyloid and tau pathology. For all comparisons, we used age as the null model, performing DeLong\u2019s tests to evaluate the performance of age relative to biomarker-based prediction.<\/jats:p>\n                  <jats:p>Imaging biomarkers increased at around 40 years old, with plasma pTau217 increasing somewhat later than the three PET biomarkers. Striatal amyloid increased before cortical amyloid in some participants; however, this was not uniform across individuals. If an individual was classified as a reliable accumulator with one biomarker, he or she was likely to be a reliable accumulator in other biomarkers. Age was as sensitive as plasma pTau217 in its ability to both detect preclinical Alzheimer's disease pathology and predict near future accumulation of both amyloid and tau.<\/jats:p>\n                  <jats:p>These results suggest that all adults with Down syndrome should be screened for Alzheimer\u2019s disease pathology starting shortly before age 40 years and considered for clinical trials. Age alone was as effective at detecting both current pathology and likely future accumulation as plasma pTau217. Because this disease is so closely concurrent with age in individuals with Down syndrome, plasma pTau217 may not provide more diagnostic benefits than age.<\/jats:p>","DOI":"10.1093\/brain\/awaf418","type":"journal-article","created":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T00:00:02Z","timestamp":1762646402000},"page":"1944-1957","source":"Crossref","is-referenced-by-count":5,"title":["Imaging and plasma biomarkers for pathological accumulation in Down syndrome"],"prefix":"10.1093","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3624-2784","authenticated-orcid":false,"given":"Julie K","family":"Wisch","sequence":"first","affiliation":[{"name":"Department of Neurology, Washington University in St. Louis , St. Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqiao","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Washington University in St. Louis , St. Louis, MO 63130 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James T","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University in St. Louis , St. Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann D","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Pittsburgh , Pittsburgh, PA 15213 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zinayida","family":"Schlachetzki","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Therapeutic Research Institute, Keck School of Medicine of USC , Los Angeles, CA 90033 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, Institute for Translational Research, University of North Texas Health Science Center , Fort Worth, TX 76107 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin L","family":"Handen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Pittsburgh , Pittsburgh, PA 15213 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley T","family":"Christian","sequence":"additional","affiliation":[{"name":"Department of Medical Physics and Psychiatry, University of Wisconsin Madison , Madison, WI 53705-2275 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Mapstone","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California Irvine School of Medicine , Orange, CA 92868-4280 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H Diana","family":"Rosas","sequence":"additional","affiliation":[{"name":"Department of Radiology, Harvard Medical School, Massachusetts General Hospital , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Neurology, Harvard Medical School, Massachusetts General Hospital , Boston, MA 02114 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph H","family":"Lee","sequence":"additional","affiliation":[{"name":"G. H. Sergievsky Center, Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, Columbia University Irving Medical Center , New York, NY 10033 ,","place":["USA"]},{"name":"Department of Neurology, Columbia University Irving Medical Center , New York, NY 10033 ,","place":["USA"]},{"name":"Department of Epidemiology, Columbia University Irving Medical Center , New York, NY 10032 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon J","family":"Krinsky-McHale","sequence":"additional","affiliation":[{"name":"Department of Psychology, New York State Institute for Basic Research in Developmental Disabilities , Staten Island, NY 10314 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick A","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sanders-Brown Center on Aging, University of Kentucky College of Medicine , Lexington, KY 40536 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan P","family":"Harp","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sanders-Brown Center on Aging, University of Kentucky College of Medicine , Lexington, KY 40536 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christy","family":"Hom","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California Irvine School of Medicine , Orange, CA 92868-4280 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira T","family":"Lott","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California Irvine School of Medicine , Orange, CA 92868-4280 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigan","family":"Hartley","sequence":"additional","affiliation":[{"name":"Waisman Center, University of Wisconsin , Madison, WI 53705 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahid","family":"Zaman","sequence":"additional","affiliation":[{"name":"Cambridge Intellectual and Developmental Disabilities Research Group, University of Cambridge , Cambridge, CB2 8AH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Ptomey","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Kansas Medical Center , Kansas City, KS 66160 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M","family":"Burns","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Kansas Medical Center , Kansas City, KS 66160 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Tudorascu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Pittsburgh , Pittsburgh, PA 15213 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2381-7059","authenticated-orcid":false,"given":"Laura","family":"Ibanez","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University in St. Louis , St. Louis, MO 63110 ,","place":["USA"]},{"name":"Department of Psychiatry, Washington University in St. Louis , St. Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S","family":"Rafii","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Therapeutic Research Institute, Keck School of Medicine of USC , Los Angeles, CA 90033 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1115-6396","authenticated-orcid":false,"given":"Elizabeth","family":"Head","sequence":"additional","affiliation":[{"name":"Department of Pathology, Gillespie Neuroscience Research Facility, University of California-Irvine , Irvine, CA 92617 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beau M","family":"Ances","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University in St. Louis , St. Louis, MO 63110 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,11,5]]},"reference":[{"key":"2026060310565620600_awaf418-B1","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.neurobiolaging.2004.08.005","article-title":"Alzheimer disease and Down syndrome: Factors in pathogenesis","volume":"26","author":"Lott","year":"2005","journal-title":"Neurobiol Aging"},{"key":"2026060310565620600_awaf418-B2","first-page":"e12062","article-title":"The AT(N) framework for Alzheimer\u2019s disease in adults with Down syndrome","volume":"12","author":"Rafii","year":"2020","journal-title":"Alzheimers 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