MAPT and Alzheimer disease: In AD brains, both 3R and 4R tau isoforms are accumulated in a hyperphosphorylated state as pathological inclusions called neurofibrillary tangles and neuropil threads, mainly in neuronal cells (Goedert, 1993; Goedert et al., 1996; Serrano-Pozo et al., 2011; Iqbal et al., 2016).