The aim of this study was to develop and validate novel t-tau immunoassays targeting N-terminal and mid-region epitopes using Simoa technology and subsequently investigate the levels of these new biomarkers versus clinically validated mid-region t-tau, p-tau and N-p-tau assays in CSF in clinical cohorts across the Alzheimer’s disease continuum, as well as across other neurological diseases including those known for high (e.g. CJD and a heterogeneous group of other acute neurological disorders) and normal (e.g. progressive supranuclear palsy) t-tau levels. This evidence concerns the gene MAPT and early-onset autosomal dominant Alzheimer disease.