Electrochemical biosensor for early Alzheimer's detection and patient risk stratification using plasma exosomes

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...

Descripción completa

Detalles Bibliográficos
Autores: Rossi, Rosanna|||0000-0002-3656-2908, Cano, Amanda|||0000-0001-9567-4283, Pallarès-Rusiñol, Arnau|||0000-0001-9990-148X, Ruiz Laza, Agustín|||0000-0003-2633-2495, Martí, Mercè|||0000-0002-1846-0043, Pividori, María Isabel|||0000-0002-5266-7873
Tipo de recurso: artículo
Fecha de publicación:2026
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:321903
Acceso en línea:https://ddd.uab.cat/record/321903
https://dx.doi.org/urn:doi:10.1016/j.bios.2025.118061
Access Level:acceso abierto
Palabra clave:Alzheimer's disease
BACE-1
Brain-derived exosomes
Electrochemical biosensor
Liquid biopsy
NLGN3
Descripción
Sumario: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.