Tau is a microtubule-stabilizing protein primarily localized in central nervous system neurons but also expressed at low levels in astrocytes and oligodendrocytes. Tau consists of six isoforms in the human brain with molecular weights of 48,000 to 67,000 daltons, depending on isoform. The antibodies used in the Simoa mouse Tau Discovery assay recognize epitopes 207–214 and 174–184 of the murine sequence (epitopes 218–225 and 185–195 of the human sequence) as described by J Schelle et al.* Tau elevation is observed in the cerebrospinal fluid (CSF) of patients with neuro-degenerative disease and severe head injuries, suggesting its extracellular release during neuronal damage and a role as a biomarker with specificity for brain injury. In Alzheimer’s disease (AD) and related neurodegenerative diseases, including chronic traumatic encephalopathy, tau is abnormally phosphorylated and aggregated into bundles of filaments. It is currently unclear whether these tau aggregates are a primary causative factor in the disease etiology. Potential movement of elevated CSF tau across the blood-brain barrier presents a possibility that measuring tau in blood could provide a convenient peripheral window into brain/CSF status.