Progress in Defining Blood Biomarkers for Alzheimer's Disease Based on Biochemical Mass Spectrometry Platforms

ABSTRACT Alzheimer's disease (AD) is the most common neurodegenerative disease globally and presents a significant challenge to the aging population of China. Early diagnosis and intervention are core to delaying disease progression; however, the early stages of AD manifest in subtle behavioral changes and are difficult to detect. The pathophysiological mechanisms of AD are characterized by amyloid beta (Aβ) deposition and abnormal tau protein phosphorylation. Current detection methods, such as positron emission tomography (PET) imaging and cerebrospinal fluid (CSF) analysis, are limited in clinical application because of high costs and the invasive nature of CSF collection. Consequently, blood biomarkers of AD are urgently sought because they are minimally invasive and cost effective. Biochemical mass spectrometry methods, such as immunoprecipitation‐mass spectrometry and liquid chromatography‐tandem mass spectrometry can precisely detect low‐abundance biomarkers. These platforms boast sensitivities at the femtogram/milliliter level with specificities exceeding 99%, and are capable of simultaneously quantifying multiple markers. For example, the plasma Aβ42/Aβ40 ratio [area under the curve = 0.967] and plasma p‐tau217 [correlation coefficient with CSF = 0.891] have demonstrated diagnostic performance comparable to PET/CSF but at a fifth to one tenth of the cost, making them viable diagnostic markers for AD. This review examines the significance and the domestic and international research status of AD blood biomarkers based on biochemical mass spectrometry platforms, and outlines the challenges and prospects for their future clinical application.