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Diagnosis of AD onset in people with DS can be challenging due to the variable degrees of intellectual disability and cognitive impairment among individuals.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Plasma samples from individuals with DS diagnosed with AD dementia (<jats:italic>n<\/jats:italic>\u00a0=\u00a033), prodromal AD (<jats:italic>n<\/jats:italic>\u00a0=\u00a031), or cognitively stable (<jats:italic>n<\/jats:italic>\u00a0=\u00a043) were enriched for neuron\u2010derived extracellular vesicles (NDEV) using immunocapture with the L1CAM antibody. We used single\u2010molecule array technology to quantify amyloid\u2010\u03b2 (A\u03b2) peptides, Tau, phosphorylated Tau, neurofilament light chain (NfL), and synaptosomal\u2010associated protein 25 (SNAP25) across diagnostic groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>NDEV levels of A\u03b240, A\u03b242, Tau, pTauT181, pTauT231, NfL, and SNAP25 were significantly higher in people with DS diagnosed with prodromal AD compared to those with no cognitive decline. Middle\u2010aged or older women had higher levels of NDEV biomarkers compared to males.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>NDEV biomarker levels can inform on the onset of AD in individuals with DS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Diagnosis of Alzheimer's dementia in individuals with Down syndrome (DS)is challenging.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Neuron\u2010derived extracellular vesicles were enriched from plasma of adults with Down syndrome.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Alzheimer's disease biomarkers were measured using single molecule array technology.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>NDEV biomarkers accurately predicted the prodromal stage of dementia in people with DS.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.70380","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T02:04:57Z","timestamp":1750125897000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Cargo of small extracellular vesicles from neuronal origin shows progression of dementia in individuals with Down syndrome"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6232-7672","authenticated-orcid":false,"given":"Aur\u00e9lie","family":"Ledreux","sequence":"first","affiliation":[{"name":"Department of Neurosurgery School of Medicine University of Colorado Anschutz Medical Campus  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Carmona\u2010Iragui","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit Department of Neurology Hospital de la 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