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27 reviewsA blood biomarker-based staging system for Alzheimer’s disease (AD) could improve the diagnosis, prognosis and identifcation of individuals most likely to beneft from specifc therapies. Here, using targeted mass spectrometry, we measured six phosphorylated and six nonphosphorylated tau peptides in plasma from two independent cohorts: BioFINDER-2 and TRIAD (n = 689). We also analyzed the ratios of phosphorylated to nonphosphorylated peptides. Our results revealed that specifc tau species became abnormal at diferent points along the disease continuum. Based on these fndings, we developed a data-driven, blood-based staging model that demonstrated strong consistency across cohorts (>85% agreement in ≥90% initializations) and refected changes in other AD biomarkers. These plasma-based stages were associated with clinical diagnoses, positron emission tomography-based stages and distinct patterns of longitudinal disease progression, including Aβ- and tau-positron emission tomography uptake, atrophy and cognitive decline. This study highlights the potential of tau blood-based biomarkers for biological staging in AD, ofering a scalable tool for tracking disease progression and guiding clinical decisions.