Detection of Plasma Biomarkers Using Immunomagnetic Reduction: A Promising Method for the Early Diagnosis of Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common form of dementia. The development of assay technologies able to diagnose early-stage AD is important. Blood tests to detect biomarkers, such as amyloid and total Tau protein, are among the most promising diagnostic methods due to their low cost, low risk, and ease of operation. However, such biomarkers in blood occur at extremely low levels and are difficult to detect precisely. In the early 2000s, a highly sensitive assay technology, immunomagnetic reduction (IMR), was developed. IMR involves the use of antibody-functionalized magnetic nanoparticles dispersed in aqueous solution. The concentrations of detected molecules are converted to reductions in the ac magnetic susceptibility of this reagent due to the association between the magnetic nanoparticles and molecules. To achieve ultra-high sensitivity, a high-Tc superconducting-quantum-interference-device (SQUID) ac magnetosusceptometer was designed and applied to detect the tiny reduction in the ac magnetic susceptibility of the reagent. Currently, a 36-channeled high-Tc SQUID-based ac magnetosusceptometer is available. Using the reagent and this analyzer, extremely low concentrations of amyloid and total Tau protein in human plasma could be detected. Further, the feasibility of identifying subjects in early-stage AD via assaying plasma amyloid and total Tau protein is demonstrated. The results show a diagnostic accuracy for prodromal AD higher than 80% and reveal the possibility of screening for early-stage AD using SQUID-based IMR.