Threonine 181 is one of the phosphorylation sites of human tau protein (pTau-181). Tau is a microtubule- stabilizing protein primarily localized in neurons of the central nervous system 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 Simoa pTau-181 Advantage V2 assay targets the proline rich region of the Tau protein which is highly conserved amongst these isoforms. Tau elevation is observed in the cerebrospinal fluid (CSF) of patients with neurodegenerative 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. pTau 181 has been found to be more strongly associated with markers of AD than total tau.