Advances in blood‐based phosphorylated tau protein biomarkers and their detection technology for Alzheimer's disease

Abstract Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized primarily by memory loss and impaired cognitive function. With the aging world population, the incidence of AD is rising, imposing substantial medical and economic burdens on society. Current diagnostic methods for AD predominantly rely on imaging studies and cerebrospinal fluid analysis, which has limitations such as complex operation and high costs. Therefore, the development of minimally invasive, convenient, and accessible blood‐based biomarkers for AD has become a research hotspot. Phosphorylated tau protein (p‐tau) plays a crucial role in AD, and its abnormal phosphorylation is closely related to the pathogenesis of the disease. This paper highlights the potential applications of three specific phosphorylated tau proteins—p‐tau217, p‐tau181, and p‐tau231—in the early diagnosis, differential diagnosis, and disease progression monitoring of AD, aiming to provide a reference for future research and clinical applications. Furthermore, the paper reviews the advancements in various ultrasensitive detection technologies for blood‐based p‐tau protein measurement. The application of these technologies has significantly enhanced the sensitivity and specificity of detection, making it feasible to detect low concentrations of blood p‐tau proteins, thereby advancing research in the early diagnosis and monitoring of AD.