Bead‐based electrochemical gap sensors for detection of tau protein in blood to diagnosis and monitoring the tauopathy

Abstract Background Recently, there is a need for a method for detecting biomarkers in blood that can be collected relatively easily for diagnosis and monitoring of dementia symptoms in Alzheimer's disease (AD) patients. Tau protein, a typical hallmark of AD, has six isoforms, and is divided into four repeating microtubule binding domains (4R) and three microtubule binding domains (3R) depending on whether exon 10 is included. According to the balance of 3R‐ and 4R‐tau, tauopathy can be distinguished. It is expected to be able to differentiate normal (NC) from AD and other dementias by measuring the tau protein in the blood. Method In this study, an electrochemical sensor with a novel structure was employed to detect tau in the plasma of living patients. The nanogap sensor consists of a gap electrode and a SU‐8 microwell for loading a single magnetic bead (Figure 1). A sample was prepared by reacting the surface of the magnetic beads with an antibody (total tau or anti 3R‐ or 4R‐tau antibody) and an antibody functionalized with a secondary O‐glycosylated tau (O‐g tau) antibody or phosphorylated tau (p‐tau) antibody. Result As a result of O‐g/p‐tau measurement, the impedance change by O‐g tau was large in NC (n=4), whereas the impedance change by p‐tau was large in AD (n=13). Patients with idiopathic Parkinson's disease (IPD) (n=3) also had more impedance changes due to p‐tau (Figure 2). As a result of measuring 3R‐ or 4R‐tau protein, the impedance change by 4R‐tau in NC was larger than that by 3R‐tau, whereas the opposite result was shown in AD. similar to the previous results, the impedance change by 3R‐tau was larger in IPD (Figure 3), Conclusion We used a novel electrochemical gap sensor to detect tau protein in blood samples collected from living patients. As a result, it is expected to be able to differentiate NC from tauopathy and other dementias by measuring the tau protein in the blood (Figure 4).