Detection of dementia (Alzheimer’s disease) marker tau using a four gold microband electrode impedance sensor

Alzheimer’s disease (AD) is the most common form of dementia, with an estimated 37 million sufferers worldwide and expected to affect 115 million by 2050. At present, there is no reliable technique or method for the diagnosis of AD in the early stages. There is an urgent demand to produce a reliable, cost-effective, objective testing and monitoring method in order to diagnose and then indicate treatment of Alzheimer’s Disease. This study presents for the first time a four-electrode impedimetric biosensor system for the detection of tau protein, which is one of the most sensitive markers for the prediction of Alzheimer’s and the level of this marker in the plasma has been found to correlate with cerebro-spinal fluid (CSF) load. The biosensor is based on the formation of stable antibody–antigen complexes on golden microband electrodes covered with a layer of a self-assembled monolayer (SAM) and protein G. Specific antibodies were immobilized on the surface of the gold electrode by interacting with protein G. Electrochemical impedance spectroscopy (EIS), where the impedance is measured as a function of frequency, was employed to analyze the impedance change, which revealed a linear response when the antigens/biomarkers bind to the antibodies with increasing concentrations. The assay is fast (30 mins for incubation and measurement) and very sensitive. The biosensor system demonstrated that it could detect the concentration down to 0.2 pM for the full-length 2N4R tau protein which is clinically relevant. This concentration is unaltered when the assay was processed in bovine serum albumin or human serum and is significantly below the detection limit of conventional detection methods such as ELISAs as demonstrated in this study. The specificity of the biosensor explored in this project was confirmed by means of Western blotting.
This method could be adapted for the detection of an array of biomarkers to provide a multiple assay which could increase the specificity and accuracy for the diagnosis of AD. The future commercialization of the biosensor system could be a revolutionary improvement for the early diagnosis and monitoring of AD progression in a point of care setting.