Abstract:

Alzheimer's disease (AD), as the primary cause of dementia among the elderly globally, has become a serious public health challenge. However, traditional cerebrospinal fluid (CSF) testing and positron emission tomography (PET) are difficult to implement for large-scale population screening and tiered diagnosis due to their invasiveness, high cost, and limited accessibility, thereby limiting the widespread adoption of early diagnosis. Blood-based biomarkers (BBMs), with their advantages of being non-invasive, low-cost, and easily deployable, have become a crucial breakthrough for early AD screening and diagnosis. Studies have shown that core BBMs, such as plasma phosphorylated tau (p-tau) and the Aβ42/Aβ40 ratio, demonstrate high clinical value in early screening and diagnosis. In primary care settings, the combination of p-tau217 and the Aβ42/Aβ40 ratio (APS2) achieves a diagnostic accuracy of 88%-92% for AD, which is significantly higher than that of conventional clinical diagnosis (61%-73%). In predicting cognitive decline, the explanatory power of plasma p-tau217 (R²=0.33) is close to that of tau-PET (R²=0.34). Furthermore, BBMs (such as p-tau217) show great potential in monitoring the efficacy of anti-Aβ monoclonal antibodies and evaluating prognosis. Nevertheless, the clinical translation of BBMs still faces severe challenges, including assay standardization, evidence generalizability, multi-factor interference, and ethical and economic issues. This article explores the practical application of BBMs in clinical diagnosis and treatment, aiming to provide an evidence-based foundation for the transition of BBMs from research to routine clinical use and to offer a reference pathway for constructing an efficient, accessible, and precise AD diagnostic and therapeutic system.

Key words: Alzheimer's disease, Blood-based biomarkers, Early screening and diagnosis, Clinical pathway