Valle-Tamayo Natalia, Aranha Mateus Rozalem, Pérez-González Rocío, Serrano-Requena Sara, Videla Laura, Barroeta Isabel, Benejam Bessy, Chiva-Blanch Gemma, Jimenez Amanda, Busciglio Jorge, Wisniewski Thomas, Do Carmo Sonia, Álvarez-Sánchez Esther, Muñoz Laia, Bejanin Alexandre, Belbin Olivia, Alcolea Daniel, Carmona-Iragui María, Lleó Alberto, Cuello A Claudio, Fortea Juan, Dols-Icardo Oriol, Iulita M Florencia
Sant Pau Memory Unit, Hospital de la Santa Creu i Sant Pau - Biomedical Research Institute Sant Pau- Universitat Autònoma de Barcelona, Barcelona, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
Alzheimers Dement. 2025 Apr;21(4):e70137. doi: 10.1002/alz.70137.
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.
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.
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.
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.
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.
在唐氏综合征（DS）和阿尔茨海默病（AD）中，神经生长因子前体蛋白（proNGF）在大脑中积累。然而，利用血浆中神经元衍生的细胞外囊泡（NDEVs）对其进行非侵入性检测尚未得到探索。
我们纳入了139名成年DS患者（45名无症状[aDS]，94名有AD症状[sDS]）和37名健康对照者。从血浆中分离出NDEVs。通过酶联免疫吸附测定法定量proNGF和四跨膜蛋白（CD81）。我们评估了proNGF/CD81随年龄的变化、在AD连续体（aDS和sDS）中的变化，以及与脑脊液（CSF）、血浆生物标志物、情景记忆和基底前脑体积的关联。
在DS中，proNGF/CD81水平随年龄增加而升高，与对照组相比，无症状和有症状个体的NDEVs中该水平更高，有症状组中最高。ProNGF与CSF磷酸化tau（p-tau）181、血浆p-tau217、神经丝轻链和情景记忆相关。
DS患者中NDEVs的ProNGF/CD81水平沿AD连续体升高，并与tau病理平行，表明其有潜力作为监测血浆中疾病进展的有前景的生物标志物。
在唐氏综合征（DS）中，神经生长因子前体蛋白（ProNGF）/四跨膜蛋白（CD81）比值在生命的第三个十年增加，早于阿尔茨海默病（AD）症状出现20年。与对照组相比，DS患者的proNGF/CD81浓度显著更高，与无症状AD患者相比，有症状AD的DS患者中该浓度显著升高。ProNGF/CD81浓度与tau病理和神经元损伤相关。
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