Quantitative assessment of AD markers using naked eyes: point-of-care testing with paper-based lateral flow immunoassay

Abstract Aβ 42 is one of the most extensively studied blood and Cerebrospinal fluid (CSF) biomarkers for the diagnosis of symptomatic and prodromal Alzheimer’s disease (AD). Because of the heterogeneity and transient nature of Aβ 42 oligomers (Aβ 42 Os), the development of technologies for dynamically detecting changes in the blood or CSF levels of Aβ 42 monomers (Aβ 42 Ms) and Aβ 42 Os is essential for the accurate diagnosis of AD. The currently commonly used Aβ 42 ELISA test kits usually mis-detected the elevated Aβ 42 Os, leading to incomplete analysis and underestimation of soluble Aβ 42 , resulting in a comprised performance in AD diagnosis. Herein, we developed a dual-target lateral flow immunoassay (dLFI) using anti-Aβ 42 monoclonal antibodies 1F12 and 2C6 for the rapid and point-of-care detection of Aβ 42 Ms and Aβ 42 Os in blood samples within 30 min for AD diagnosis. By naked eye observation, the visual detection limit of Aβ 42 Ms or/and Aβ 42 Os in dLFI was 154 pg/mL. The test results for dLFI were similar to those observed in the enzyme-linked immunosorbent assay (ELISA). Therefore, this paper-based dLFI provides a practical and rapid method for the on-site detection of two biomarkers in blood or CSF samples without the need for additional expertise or equipment. Graphical Abstract