MAPT and Alzheimer disease: Paired helical filaments that make up neurofibrillary tangles of affected neurons in AD are hyperphosphorylated and ubiquitinated [100], and recently have been associated within soluble U1 spliceosome components [23, 101, 102], in addition to classical hyperphosphorylated tau with this phosphorylation reducing Tau microtubule crosslinking character [103].