While sarkosyl-soluble PHFs are mainly constituted of tau protein in a hyperphosphorylated state, insoluble PHF fractions from Alzheimer's disease brains are Pronase resistant and phosphorylated tau accounts for no more than 15% of the content of such PHFs (Wischik et al., 1995). Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.