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

Sojeong Lee, Eunjung Kim, Chae-Eun Moon, Chaewon Park, Jong-Woo Lim, Minseok Baek, Moo-Kwang Shin, Jisun Ki, Hanna Cho (), Yong Woo Ji () and Seungjoo Haam ()
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Sojeong Lee: Yonsei University
Eunjung Kim: Incheon National University
Chae-Eun Moon: Yonsei University College of Medicine
Chaewon Park: Yonsei University
Jong-Woo Lim: Yonsei University
Minseok Baek: Yonsei University Wonju College of Medicine
Moo-Kwang Shin: Yonsei University
Jisun Ki: Yonsei University
Hanna Cho: Gangnam Severance Hospital, Yonsei University College of Medicine
Yong Woo Ji: Yonsei University College of Medicine
Seungjoo Haam: Yonsei University

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract 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 (R2 = 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.

Date: 2023
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DOI: 10.1038/s41467-023-43995-5

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