Redefining Alzheimer's disease diagnostics in the age of blood-based biomarkers

Alzheimer's disease (AD) is the primary cause of dementia and represents an increasing medical and socioeconomic burden in aging populations worldwide. The disease is characterized by progressive pathological changes, including amyloid-β deposition, tau hyperphosphorylation, synaptic dysfunction, and widespread neurodegeneration, which develop long before clinical symptoms become evident. While cerebrospinal fluid biomarkers and positron emission tomography imaging have significantly improved biological diagnosis and disease staging, their invasive nature, high cost, and limited accessibility constrain routine clinical application. As a result, blood-based biomarkers have gained attention as minimally invasive and scalable alternatives. This chapter summarizes the evolution and current landscape of blood-derived biomarkers for AD, covering amyloid-related measures, phosphorylated tau species, neurofilament light chain as an indicator of neurodegeneration, and emerging markers of neuroinflammation and synaptic dysfunction. Recent advances in ultrasensitive assays and analytical standardization have improved their clinical reliability, positioning blood-based biomarkers as valuable tools for early detection, disease monitoring, and therapeutic decision-making.