Cargo of small extracellular vesicles from neuronal origin shows progression of dementia in individuals with Down syndrome
Ledreux, A. (University of Colorado Anschutz Medical Campus)
Carmona Iragui, Maria (Institut de Recerca Sant Pau)
Videla Toro, Laura (Institut de Recerca Sant Pau)
Benejam, Bessy (Fundació Catalana Síndrome de Down)
Barroeta, Isabel (Institut de Recerca Sant Pau)
Lleó, Alberto (Institut de Recerca Sant Pau)
Alcolea, Daniel (Institut de Recerca Sant Pau)
Fortea, Juan (Institut de Recerca Sant Pau)
Universitat Autònoma de Barcelona. Departament de Medicina

Fecha:	2025
Resumen:	INTRODUCTION: Individuals with Down syndrome (DS) are at an ultra-high risk of developing Alzheimer's disease (AD). Diagnosis of AD onset in people with DS can be challenging due to the variable degrees of intellectual disability and cognitive impairment among individuals. METHODS: Plasma samples from individuals with DS diagnosed with AD dementia (n = 33), prodromal AD (n = 31), or cognitively stable (n = 43) were enriched for neuron-derived extracellular vesicles (NDEV) using immunocapture with the L1CAM antibody. We used single-molecule array technology to quantify amyloid-β (Aβ) peptides, Tau, phosphorylated Tau, neurofilament light chain (NfL), and synaptosomal-associated protein 25 (SNAP25) across diagnostic groups. RESULTS: NDEV levels of Aβ40, Aβ42, 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-aged or older women had higher levels of NDEV biomarkers compared to males. DISCUSSION: NDEV biomarker levels can inform on the onset of AD in individuals with DS. Highlights: Diagnosis of Alzheimer's dementia in individuals with Down syndrome (DS)is challenging. Neuron-derived extracellular vesicles were enriched from plasma of adults with Down syndrome. Alzheimer's disease biomarkers were measured using single molecule array technology. NDEV biomarkers accurately predicted the prodromal stage of dementia in people with DS.
Ayudas:	Instituto de Salud Carlos III PI20/01473 Instituto de Salud Carlos III PI18/00335 Instituto de Salud Carlos III PI23/01786 Instituto de Salud Carlos III PI22/00785
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Alzheimer's disease ; Down syndrome ; Amyloid-beta ; Biomarker ; Dementia ; Extracellular vesicle ; Neurofilament-light ; Phosphorylated Tau
Publicado en:	Alzheimer's & dementia, Vol. 21 Núm. 6 (june 2025) , p. e70380, ISSN 1552-5279

DOI: 10.1002/alz.70380
PMID: 40524460

11 p, 1.8 MB

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