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therapeutic treatment windows in DS.<\/jats:p>\n                  <jats:p>In this study, 198 adults with DS from the Alzheimer Biomarker Consortium\u2013Down Syndrome and 172 neurotypical adults from the Wisconsin Registry for Alzheimer\u2019s Prevention with available longitudinal beta-amyloid PET, tau PET and plasma p-tau217 analysed on the Lilly Meso Scale Delivery Platform were included.<\/jats:p>\n                  <jats:p>Individuals with DS had a significantly higher lifetime risk of beta-amyloid plaque onset. Temporal modelling of longitudinal biomarker measures revealed earlier age at positivity of beta-amyloid plaques, p-tau217 and neurofibrillary tau tangles in DS relative to the neurotypical cohort. The onset of p-tau217 and tau PET positivity in DS occurred nearly simultaneously, roughly 4\u20136 years following beta-amyloid onset, whereas the neurotypical group displayed greater temporal latency between positivity of the two biomarkers.<\/jats:p>\n                  <jats:p>The early and simultaneous onset of these biomarkers in DS highlights the necessity for early therapeutic interventions in this population. This work, combined with the upcoming anti-amyloid safety and efficacy clinical trials for DS will help to identify optimal treatment windows for these individuals.<\/jats:p>","DOI":"10.1093\/brain\/awaf428","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T13:10:16Z","timestamp":1763125816000},"page":"2449-2462","source":"Crossref","is-referenced-by-count":2,"title":["The tau biomarker cascade is condensed in Down syndrome compared with sporadic Alzheimer\u2019s disease"],"prefix":"10.1093","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8966-8397","authenticated-orcid":false,"given":"Matthew D","family":"Zammit","sequence":"first","affiliation":[{"name":"Waisman Center, University of Wisconsin-Madison , Madison, WI 53705 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailey","family":"Bruzzone","sequence":"additional","affiliation":[{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, 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