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Characterizing neurofibrillary tangle maturity of phosphorylated tau fluid biomarkers in Alzheimer's disease

Phosphorylated tau (p‐tau) cerebrospinal fluid and plasma biomarkers have become more accurate in predicting Alzheimer’s disease (AD) pathology. Although p‐tau fluid biomarkers have been studied in vivo for nearly 20 years, tau phosphorylation sites have not been systematically studied in the context of neurofibrillary tangle maturity in the postmortem brain. Neurofibrillary tangles have a lifespan that is defined by three maturity levels: pretangles, mature tangles, and ghost tangles. Our goal was to characterize four tau phosphorylation sites (pT181, pT205, pT217, and pT231) in postmortem brain to determine which neurofibrillary tangle maturity level they preferentially recognize.