Progress in Optical Methods for the Detection of Two Core Blood Biomarkers of Alzheimer’s Disease: Amyloid-Beta and Tau Proteins

Alzheimer’s disease (AD) is the most common neurodegenerative disorder worldwide. Early diagnosis of AD is crucial for delaying disease progression and improving patients’ quality of life. Blood biomarkers, particularly amyloid-beta (Aβ) and Tau proteins along with their phosphorylated isoforms, show advantages such as convenient sampling, minimal invasiveness, and excellent repeatability. However, the extremely low concentrations of AD biomarkers in blood impose stringent requirements on the sensitivity, specificity, and anti-interference capability of detection methods. Optical methods provide promising analytical platforms to address these challenges in view of their intrinsic merits of high sensitivity and selectivity; rapid response; and potential for miniaturization. This review systematically summarizes the latest advances in optical methods for the detection of the two core AD blood biomarkers (Aβ and Tau), covering techniques such as colorimetry, fluorescence, chemiluminescence, surface plasmon resonance (SPR), and surface-enhanced Raman scattering (SERS). The sensing principles, design strategies, and analytical performances of these methods are discussed, with special emphasis on different signal amplification strategies. In addition, several challenges and future prospects are provided with a primary focus on single-molecule detection, insufficient sensitivity and stability, lack of validation with large clinical cohorts, and absence of standardization. This review aims to provide researchers with guidance for the rational development of high-performance optical methods to achieve early diagnosis of AD.