ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
Nerve growth factor precursor alterations in neuron-derived extracellular vesicles from individuals with Down syndrome along the Alzheimer's disease continuum.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed.
- Precision medicine for Alzheimer's disease in Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- The Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) and its contributions to understanding Alzheimer's disease in Down syndrome: A decade of discovery.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Nerve growth factor precursor alterations in neuron-derived extracellular vesicles from individuals with Down syndrome along the Alzheimer's disease continuum.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
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23 authors.
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Abstract
backgroundIn 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.
methodsWe 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.
resultsIn 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.
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