Tau proteoforms as plasma biomarkers in Alzheimer’s disease: mechanisms, measurement, and medicine

Blood-based tau proteoforms are poised to move Alzheimer's diagnostics from specialized imaging to accessible frontline testing, with plasma p-tau217 approaching positron emission tomography (PET) and CSF performance and multi-analyte panels with glial fibrillary acidic protein (GFAP) or neurofilament light (NfL) improving differential diagnosis while reducing invasiveness and cost. Building on the first FDA-cleared plasma assay (Lumipulse G p-tau217/Aβ1-42 Ratio) in May 2025, we anticipate a dual pathway over the next decade in which referral centers use high-plex mass spectrometry (MS) panels for phosphoforms and truncations, while primary care adopts automated high-throughput immunoassays (e.g. chemiluminescent enzyme immunoassay (CLEIA)) for triage, supported by harmonized standard operating procedures (SOPs), cross-matrix calibration, and robust reference materials.