A sensitive FRET-based HEK cell assay that measures bioactive tau, which are soluble tau species capable of inducing tau aggregation and are believed to contribute to the pathological spread of tau in the brain [31, 66], indicated bioactive tau is enriched in vessel preparations from Alzheimer’s disease (Fig. 1e) and appears to be elevated in frontotemporal lobar dementia-tau (FTLD-tau, Fig. 1f) and some control brains (Braak stages ≤ II). This evidence concerns the gene MAPT and early-onset autosomal dominant Alzheimer disease.