First-generation ligands such as AV-1451 [24] are particularly useful in Alzheimer’s disease which is associated with abnormally hyperphosphorylated and misfolded tau that contains both 3 and 4 repeats of exon 10 of the MAPT gene, so-called 3R/4R tau. This evidence concerns the gene MAPT and early-onset autosomal dominant Alzheimer disease.