Transistor Biosensors: A Path to Accessible, Minimally Invasive Early Screening for Alzheimer's Disease

Current clinical diagnostic approaches for Alzheimer's disease (AD), including positron emission tomography and cerebrospinal fluid testing, face limitations related to invasiveness, high cost, and restricted accessibility. The identification of blood biomarkers, including amyloid-β (Aβ) and phosphorylated tau (p-tau) proteins, has arisen as a potential avenue for noninvasive, scalable, and cost-effective early screening. Transistor biosensors offer a compelling technological platform in this study. Capitalizing on ultrahigh sensitivity, rapid response, label-free operation, and potential for miniaturization and integration, these devices have demonstrated effectiveness in detecting ultralow concentrations of AD pathological proteins in blood, surpassing the detection limits of conventional method. This review systematically outlines the operational mechanisms of transistor biosensors and discusses performance optimization strategies. It further summarizes transformative advances in detecting key AD biomarkers, including Aβ proteins and p-tau isoforms, and highlights innovative directions such as multiplexed biomarker detection and machine learning-assisted diagnostic interpretation. Despite persistent challenges related to interfacial functionalization, anti-interference stability, and clinical validation and standardization, the integration of transistor biosensors with microfluidics and wearable technologies presents a revolutionary technological nexus. Such integrated systems hold considerable potential to enable early risk warning, longitudinal monitoring, and precise, personalized intervention strategies for AD. Therefore, transistor biosensor represents a paradigm shift toward accessible, dynamic, and precision biomarker profiling, paving the way for next-generation AD screening and management frameworks.