Blood-based biomarkers of Alzheimer's disease: potential utility in clinical practice

Blood-based biomarkers (BBMs) for Alzheimer's disease are beginning to enter clinical practice. As this integration advances, it is essential to critically examine their strengths, limitations, and readiness for broader clinical application.

Evidence increasingly supports the utility of BBMs for clinical management of Alzheimer's disease, with phosphorylated tau species, Aβ42/40 ratio, GFAP, and NfL among the most studied. Plasma p-tau forms have emerged as the most promising markers, showing strong correlations with amyloid plaque deposition and predictive value for disease progression. The WHO and the Global CEO Initiative have outlined minimum performance criteria for clinical use. While no BBM meets these benchmarks with a single cutpoint, adopting a two-cutpoint approach by introducing an intermediate category has enabled some assays to achieve the required accuracy. Several assays are now commercially available, and two have recently received FDA clearance to assist in confirming or ruling out amyloid-beta pathology.

BBMs could transform Alzheimer's disease diagnostics by enabling scalable, minimally invasive approaches for early detection and monitoring. As implementation advances, assay harmonization, assessment of demographic and physiological influences, and real-world validation across diverse populations remain essential to ensure reliability and equitable access.