Together, our findings agree with the previously presented hypothesis that during the Alzheimer’s disease pathophysiological process, tau fragments including the N-terminus are released early by neurons that are presumably affected by Aβ toxicity but still only at risk of developing tangle pathology.11,22 We also showed that this early increase can be detected with N-terminal directed assays targeting both phosphorylated and non-phosphorylated epitopes. This evidence concerns the gene MAPT and early-onset autosomal dominant Alzheimer disease.