The clinical utility of blood-based biomarkers of Alzheimer's disease: Triumphs and pitfalls.

Alzheimer's disease is increasingly understood as a biological continuum characterized by amyloid deposition, tau pathology, neurodegeneration, and neuroinflammatory processes. Blood-based biomarkers have emerged as accessible tools for detecting these processes in peripheral circulation, offering an alternative to cerebrospinal fluid and imaging-based diagnostics. This chapter examines the clinical utility of key blood-based biomarkers, including phosphorylated tau, amyloid-β ratios, neurofilament light chain, and glial fibrillary acidic protein, within the context of current diagnostic frameworks. Phosphorylated tau, particularly p-tau217, demonstrates strong performance in identifying Alzheimer's disease-related pathology, while amyloid biomarkers contribute to early detection and risk stratification. Neurofilament light chain reflects the extent of neurodegeneration, and glial fibrillary acidic protein provides insight into astrocytic activation and inflammatory responses. The integration of these markers into combined models supports stage-specific interpretation across the disease continuum and improves diagnostic efficiency. Despite these advances, important limitations remain, including variability across analytical platforms, influence of systemic factors, and differences in performance across clinical settings. Biomarker results are inherently probabilistic and require interpretation within structured clinical pathways. Blood-based biomarkers have the potential to improve access to biological assessment and support clinical decision-making. Their effective implementation depends on continued standardization, validation across diverse populations, and integration into patient-centered care.