Amplified fluorogenic immunoassay for early diagnosis and monitoring of Alzheimer's disease from tear fluid

• Published in: Nature communications Vol. 14; no. 1; p. 8153
• Main Authors: Lee, Sojeong, Kim, Eunjung, Moon, Chae-Eun, Park, Chaewon, Lim, Jong-Woo, Baek, Minseok, Shin, Moo-Kwang, Ki, Jisun, Cho, Hanna, Ji, Yong Woo, Haam, Seungjoo
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 09.12.2023; Nature Publishing Group UK; Nature Portfolio
• Subjects: Adenylate cyclase; Alzheimer Disease - metabolism; Alzheimer's disease; Amplification; Amyloid beta-Peptides; Biomarkers; Biomarkers - metabolism; Biopsy; Diagnosis; Early Diagnosis; Humans; Immunoassay; Long-term care; Monitoring; Nanoparticles; Neurodegenerative diseases; Proteomics; Reproducibility of Results; Self-assembly; Signs and symptoms; Telemedicine
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-43995-5

Accurate diagnosis of Alzheimer's disease (AD) in its earliest stage can prevent the disease and delay the symptoms. Therefore, more sensitive, non-invasive, and simple screening tools are required for the early diagnosis and monitoring of AD. Here, we design a self-assembled nanoparticle-mediated amplified fluorogenic immunoassay (SNAFIA) consisting of magnetic and fluorophore-loaded polymeric nanoparticles. Using a discovery cohort of 21 subjects, proteomic analysis identifies adenylyl cyclase-associated protein 1 (CAP1) as a potential tear biomarker. The SNAFIA demonstrates a low detection limit (236 aM), good reliability (R  = 0.991), and a wide analytical range (0.320-1000 fM) for CAP1 in tear fluid. Crucially, in the verification phase with 39 subjects, SNAFIA discriminates AD patients from healthy controls with 90% sensitivity and 100% specificity in under an hour. Utilizing tear fluid as a liquid biopsy, SNAFIA could potentially aid in long-term care planning, improve clinical trial efficiency, and accelerate therapeutic development for AD.