Nerve growth factor precursor alterations in neuron-derived extracellular vesicles from individuals with Down syndrome along the Alzheimer's disease continuum

BACKGROUND: In Down syndrome (DS) and Alzheimer's disease (AD), nerve growth factor precursor protein (proNGF) accumulates in the brain. However, its non-invasive detection using neuron-derived extracellular vesicles (NDEVs) from plasma remains unexplored. METHODS: We included 139 adults with D...

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Detalhes bibliográficos
Autores: Valle-Tamayo, N, Aranha, MR, Pérez-González, R, Serrano-Requena, S, Videla, L, Barroeta, I, Benejam, B, Chiva-Blanch, G, Jimenez, A, Busciglio, J, Wisniewski, T, Do Carmo, S, Alvarez-Sánchez, E, Muñoz, L, Bejanin, A, Belbin, O, Alcolea, D, Carmona-Iragui, M, Lleó, A, Cuello, AC, Fortea, J, Dols-Icardo, O, Iulita, MF
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
Repositorio:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
OAI Identifier:oai:dnet:isabial_____::3b6022b6b944af46a2e29eba8159c59e
Acesso em linha:https://isabial.portalinvestigacion.com/publicaciones12514
https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.70137
Access Level:acceso abierto
Palavra-chave:Alzheimer's disease
Down syndrome
nerve growth factor precursor protein
neuronal injury
neuron-derived extracellular vesicle
tau pathology
Descrição
Resumo:BACKGROUND: In Down syndrome (DS) and Alzheimer's disease (AD), nerve growth factor precursor protein (proNGF) accumulates in the brain. However, its non-invasive detection using neuron-derived extracellular vesicles (NDEVs) from plasma remains unexplored. METHODS: We included 139 adults with DS (45 asymptomatic [aDS], 94 symptomatic for AD [sDS]) and 37 healthy controls. NDEVs were isolated from plasma. ProNGF and tetraspanin (CD81) were quantified by enzyme-linked immunosorbent assay. We assessed proNGF/CD81 changes with age, along the AD continuum (aDS and sDS), and associations with cerebrospinal fluid (CSF), plasma biomarkers, episodic memory, and basal forebrain volume. RESULTS: In DS, proNGF/CD81 levels increased with age and were higher in NDEVs from asymptomatic and symptomatic individuals compared to controls, with the highest levels in the symptomatic group. ProNGF correlated with CSF phosphorylated tau (p-tau)181, plasma p-tau217, neurofilament light chain, and episodic memory. DISCUSSION: ProNGF/CD81 levels in NDEVs increase along the AD continuum in DS and parallel tau pathology, indicating the potential as a promising biomarker for monitoring disease progression in plasma.

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