Cerebrospinal fluid and blood biomarkers in the diagnostic assays of Alzheimer's disease

The anti-amyloid-beta (anti-A beta) fibrils and soluble oligomers antibody aducanumab were approved to effectively slow down the progression of Alzheimer's disease (AD) at higher doses in 2019, reaffirming the therapeutic effects of targeting the core pathology of AD. A timely and accurate diagnosis in the prodromal or pre-dementia stage of AD is essential for patient recruitment, stratification, and monitoring of treatment effects. AD core biomarkers amyloid-beta (A beta(1-42)), total tau (t-tau), and phosphorylated tau (p-tau) have been clinically validated to reflect AD-type pathological changes through cerebrospinal fluid (CSF) measurement or positron-emission tomography (PET) and found to have high diagnostic performance for AD identification in the stage of mild cognitive impairment. The development of ultrasensitive immunoassay technology enables AD pathological proteins such as tau and neurofilament light (NFL) to be measured in blood samples. However, combined biomarker detection or targeting multiple biomarkers in immunoassays will increase detection sensitivity and specificity and improve diagnostic accuracy. This review summarizes and analyzes the performance of current detection methods for early diagnosis of AD, and provides a concept of detection method based on multiple biomarkers instead of a single target, which may become a potential tool for early diagnosis of AD in the future.