guest ::
| Home > Articles > Published articles > Nerve growth factor precursor alterations in neuron-derived extracellular vesicles from individuals with Down syndrome along the Alzheimer's disease continuum |
| Home > Articles > Published articles > Nerve growth factor precursor alterations in neuron-derived extracellular vesicles from individuals with Down syndrome along the Alzheimer's disease continuum |
(Institut de Recerca Sant Pau) (Institut de Recerca Sant Pau) (Institut de Recerca Sant Pau) (Institut de Recerca Sant Pau) (Instituto de Salud Carlos III) (Instituto de Salud Carlos III) (Institut de Recerca Sant Pau) (Institut de Recerca Sant Pau) (Institut de Recerca Sant Pau) (Institut de Recerca Sant Pau) (Institut de Recerca Sant Pau) (McGill University) (Institut de Recerca Sant Pau) (Institut de Recerca Sant Pau) (Instituto de Salud Carlos III)| Date: | 2025 |
| Abstract: | 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. Highlights: Nerve growth factor precursor protein (ProNGF)/tetraspanin (CD81) ratio increased in the third decade of life, 20 years before Alzheimer's disease (AD) symptom onset in Down syndrome (DS). proNGF/CD81 concentrations were significantly higher in individuals with DS compared to controls and were notably elevated in individuals with DS and symptomatic AD compared to asymptomatic AD. proNGF/CD81 concentrations were associated with tau pathology and neuronal injury. |
| Grants: | Instituto de Salud Carlos III PI23/01786 Instituto de Salud Carlos III PI20/01330 Instituto de Salud Carlos III PI18/00435 Instituto de Salud Carlos III PI22/00307 Instituto de Salud Carlos III PI20/01473 Instituto de Salud Carlos III PI21/01395 European Commission H2020-SC1-BHC-2018-2020 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Alzheimer's disease ; Down syndrome ; Nerve growth factor precursor protein ; Neuronal injury ; Neuron-derived extracellular vesicle ; Tau pathology |
| Published in: | Alzheimer's & dementia, Vol. 21 Núm. 4 (april 2025) , p. e70137, ISSN 1552-5279 |
