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

Aβ 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 oligomers (AβOs), the development of technologies for dynamically detecting changes in the blood or CSF levels of Aβ monomers (AβMs) and AβOs is essential for the accurate diagnosis of AD. The currently commonly used Aβ ELISA test kits usually mis-detected the elevated AβOs, leading to incomplete analysis and underestimation of soluble Aβ, resulting in a comprised performance in AD diagnosis. Herein, we developed a dual-target lateral flow immunoassay (dLFI) using anti-Aβ monoclonal antibodies 1F12 and 2C6 for the rapid and point-of-care detection of AβMs and AβOs in blood samples within 30 min for AD diagnosis. By naked eye observation, the visual detection limit of AβMs or/and AβOs 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.