Overview in Electrochemical and Electrical Biosensors for Determining Blood Protein Biomarkers of Alzheimer’s Disease

Early diagnosis of Alzheimer’s disease (AD) can facilitate the establishment and implementation of therapeutic interventions. The currently used diagnosis methods for AD mainly include cerebrospinal fluid analysis and positron emission tomography imaging. Due to their high invasiveness, high cost, and limited accessibility, these technologies are difficult to meet the needs of large-scale population screening, grading diagnosis, and treatment, thereby limiting the popularization of early diagnosis of AD. The detection of blood biomarkers has become an important breakthrough in early screening and diagnosis of different diseases due to its non-invasive, low-cost, and easy-to-operation advantages. Recently, blood proteins such as amyloid-beta (Aβ), total and phosphorylated Tau, light chain neurofilaments (NFL), and glial fibrillary acidic protein (GFAP) have been considered promising biomarkers for the diagnosis of AD. However, there is currently no effective, minimally invasive, and easily accessible detection method for clinical diagnosis and risk prediction of AD. Electrochemical and electrical biosensors are highly sensitive, simple, fast, and cost-effective analytical tools for disease monitoring, drug development, and target detection. In this work, we comprehensively and systematically overview the progress of various electrochemical and electrical techniques for determining AD-related blood protein biomarkers, mainly including electrochemistry, electrochemiluminescence, photoelectrochemistry, quartz crystal microbalance, field-effect transistor, and organic electrochemical transistor. This work can provide guidance for researchers to develop novel electrochemical and electrical biosensors for early and accurate diagnosis of AD.