Progress regarding the context-of-use of tau as biomarker of Alzheimer's disease and other neurodegenerative diseases.

Introduction Tau protein misfolding and accumulation in toxic species is a critical pathophysiological process of Alzheimer's Disease (AD) and other neurodegenerative disorders (NDDs). Tau biomarkers, namely cerebrospinal fluid (CSF) total-tau (t-tau), 181-phosphorylated tau (p-tau) and tau-PET tracers, have been recently embedded in the diagnostic criteria for AD. Nevertheless, the role of tau as a diagnostic and prognostic biomarker for other NDDs remains controversial. Areas covered We performed a systematical PubMed-based review of the most recent advances in tau-related biomarkers for NDDs. We focused on papers published from 2015 to 2020 assessing the diagnostic or prognostic value of each biomarker. Expert opinion The assessment of tau biomarkers in alternative easily accessible matrices, through the development of ultrasensitive techniques, represents the most significant perspective for AD-biomarker research. In NDDs, novel tau isoforms (e.g., p-tau217) or proteolytic fragments (e.g., N-terminal fragments) may represent candidate diagnostic and prognostic biomarkers and may help monitoring disease progression. Protein misfolding amplification assays, allowing the identification of different tau strains (e.g. 3R- vs. 4R-tau) in CSF, may constitute a breakthrough for the in vivo stratification of NDDs. Tau-PET may help tracking the spatial-temporal evolution of tau pathophysiology in AD but its application outside the AD-spectrum deserves further studies.