MAPT and Alzheimer disease: Numerous recent studies have linked these soluble aggregates to the initiation and development of AD—not the large, insoluble Aβ deposits in extraneuronal neuritic plaques or the insoluble phospho-tau deposits that comprise intraneuronal neurofibrillary tangles [4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21].