Electrochemical biosensor for early Alzheimer's detection and patient risk stratification using plasma exosomes
Rossi, Rosanna (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Cano, Amanda (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Pallarès-Rusiñol, Arnau (Universitat Autònoma de Barcelona. Departament de Química)
Ruiz Laza, Agustín (Ace Alzheimer Center Barcelona)
Martí, Mercè (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Pividori, María Isabel (Universitat Autònoma de Barcelona. Departament de Química)

Data:	2026
Descripció:	9 pàg.
Resum:	Alzheimer's Disease (AD) is the leading cause of dementia, accounting for 60-70 % of cases worldwide. Early diagnosis remains challenging due to the limitations of current diagnostic tools, which are costly, invasive, and suffer from low patient compliance. Blood-based biomarkers, particularly plasma brain-derived exosomes (BDEs), have emerged as a promising alternative since they carry AD-related molecules and can be isolated non-invasively. In this study, an immunoassay was developed to isolate BDEs using magnetic particles functionalized with an anti-neuroligin-3 (NLGN3) antibody, while the AD-related marker β-secretase (BACE-1) was detected on the captured exosomes. This is the first report combining NLGN3 for for the isolation of BDEs with BACE-1 as a detection target, establishing a novel biomarker panel for AD diagnostics. The assay was evaluated across three readout platforms-optical, chemiluminescent, and electrochemical-with detection limits in the range of 104-105 exosomes μL-1. Among them, the portable electrochemical platform achieved the improved LOD (1. 51 × 104 exosomes μL-1, R2 = 0. 9829). Plasma samples from patients with AD, mild cognitive impairment (MCI), and healthy controls were analyzed, revealing differences in exosomal BACE-1 levels (p < 0. 1, t-test). These findings demonstrate, for the first time, an in vitro diagnostic approach based on a portable electrochemical biosensor for early AD detection in plasma through a novel exosomal biomarker panel. Compared to conventional diagnostics, this biosensor offers a non-invasive and cost-effective solution for AD screening, with the potential to support earlier intervention and patient risk stratification.
Ajuts:	Agencia Estatal de Investigación PDC2022-133363-I00 Agencia Estatal de Investigación PID2021-122473OA-I00 Ministerio de Educación, Cultura y Deporte FPU16/01579 Instituto de Salud Carlos III CB18/05/00010 Instituto de Salud Carlos III CD22/00125
Nota:	Altres ajuts: acords transformatius de la UAB
Drets:	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, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Alzheimer's disease ; BACE-1 ; Brain-derived exosomes ; Electrochemical biosensor ; Liquid biopsy ; NLGN3
Publicat a:	Biosensors & bioelectronics, Vol. 292 (January 2026) , art. 118061, ISSN 1873-4235

DOI: 10.1016/j.bios.2025.118061
PMID: 41061470

9 p, 3.3 MB

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