Moreover, recent studies on mass spectrometric analyses of sarkosyl-insoluble and protease-resistant tau filaments from human brain with AD and cryo-electron microscopic analyses demonstrated that the protease-resistant cores of tau filaments contained abundant residues of the exon 11–12, which is proposed to adopt a combined cross- β/ β-helix structure with two identical protofilaments, as well as over a dozen of residues on the C-terminal side of exon 10 (4R tau) and exon 9 (3R tau), which exhibit unsharpened density on cryo-electron microscopy like a less ordered β-sheet [14, 48]. Here, MAPT is linked to Alzheimer disease.