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(DSAD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We analyzed \u03b1Syn\u2010SAA in cerebrospinal fluid (CSF) from 270 adults with Down syndrome, from the Down Alzheimer Barcelona Neuroimaging Initiative and from the AD21 cohort from the Department of Neurology at the University Hospital, Ludwig Maximilian University of Munich, Germany. Neuropathological examinations were conducted in 19 brain donors (five with\n                      <jats:italic>ante mortem<\/jats:italic>\n                      CSF). Participants were classified as asymptomatic or symptomatic (prodromal\/dementia) Alzheimer's disease (AD). CSF A\u03b21\u201042\/1\u201040, CSF and plasma p\u2010Tau181, and neurofilament light chain (NfL) levels were measured. Neuropathological evaluations assessed AD neuropathological changes and Lewy body pathology (LBP).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      \u0391Syn\u2010SAA was positive in 9.2% of cases, independent of age or cognitive status. Symptomatic \u03b1Syn\u2010positive cases exhibited higher plasma NfL levels than \u03b1Syn\u2010negative cases (31\u00a0vs 21\u00a0pg\/mL,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.027). LBP was observed in 47% of necropsies. The individual with severe neocortical LBP was \u03b1Syn\u2010SAA\u2010positive.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These findings highlight LBP prevalence in DSAD but suggest current SAA may fail to detect limited \u03b1Syn deposition.<\/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>\u03b1Syn\u2010SAA positivity in DSAD is 9.2%, similar to ADAD but lower than sporadic AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Misfolded \u03b1Syn was detectable from early ages in individuals with DS.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Positivity rates did not vary with age or clinical status in DS.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Plasma NfL levels are higher in symptomatic \u03b1Syn\u2010SAA positive versus negative cases.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>CSF \u03b1Syn seeding activity was associated with high neocortical LBP at necropsy.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70342","type":"journal-article","created":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T10:39:28Z","timestamp":1751193568000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Alpha\u2010synuclein co\u2010pathology in Down syndrome\u2010associated Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Alexander Maximilian","family":"Bernhardt","sequence":"first","affiliation":[{"name":"Department of Neurology Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  Munich Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), site Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3039-9115","authenticated-orcid":false,"given":"\u00cd\u00f1igo","family":"Rodr\u00edguez\u2010Baz","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armin","family":"Giese","sequence":"additional","affiliation":[{"name":"MODAG GmbH, Mikroforum Ring 3  Wendelsheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Matthias","sequence":"additional","affiliation":[{"name":"Aesku.Diagnostics GmbH  Wendelsheim Germany"},{"name":"MODAG GmbH, Mikroforum Ring 3  Wendelsheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bessy","family":"Benejam","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology Hospital de la Santa Creu i Sant Pau Institut de Recerca Sant Pau (IR SANT PAU)  Barcelona Spain"},{"name":"Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III  Madrid Spain"},{"name":"Barcelona Down Medical Center Fundaci\u00f3 Catalana de S\u00edndrome de Down  Barcelona 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