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While monoclonal antibodies (mAbs) targeting amyloid are approved for older AD patients, their efficacy in DS remains unexplored. This study examines amyloid positron emission tomography (PET) positivity (A+), memory function, and clinical status across ages in DS to guide mAb trial designs.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Cross\u2010sectional data from the Alzheimer Biomarker Consortium\u2013Down Syndrome (ABC\u2010DS) was analyzed. PET amyloid beta in Centiloids classified amyloid status using various cutoffs. Episodic memory was assessed using the modified Cued Recall Test, and clinical status was determined through consensus processes.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Four hundred nine DS adults (mean age\u00a0=\u00a044.83 years) were evaluated. A+ rates increased with age, with mean amyloid load rising significantly. Memory decline and cognitive impairment are also correlated with age.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>These findings emphasize the necessity of tailoring mAb trials for DS, considering age\u2010related AD characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>There is rapid increase in prevalence of amyloid beta (A\u03b2) positron emission tomography (PET) positivity in Down syndrome (DS) after the age of 40 years.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>A\u03b2 PET positivity thresholds have significant impact on prevalence rates in DS.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>There is a significant lag between A\u03b2 PET positivity and clinical symptom onset in DS.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14068","type":"journal-article","created":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T09:14:14Z","timestamp":1719566054000},"page":"5570-5577","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Assessing amyloid PET positivity and cognitive function in Down syndrome to guide clinical trials targeting amyloid"],"prefix":"10.1002","volume":"20","author":[{"given":"Sophia","family":"Krasny","sequence":"first","affiliation":[{"name":"Scripps Research Institute  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University  Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigan L.","family":"Hartley","sequence":"additional","affiliation":[{"name":"Waisman Center University of Wisconsin  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben L.","family":"Handen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie K.","family":"Wisch","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University  Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna H.","family":"Boehrwinkle","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University  Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beau M.","family":"Ances","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University  Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Rafii","sequence":"additional","affiliation":[{"name":"Alzheimer's Therapeutic Research Institute Keck School of Medicine of University of Southern California  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the ABC\u2010DS 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