For example, we previously discovered that a core component of the spliceosome complex, U1 small ribonucleoprotein 70 kDa (U1-70K), becomes insoluble in both symptomatic and early pre-symptomatic stages of AD where individuals had high brain amyloid pathology, yet were cognitively normal at death (Bai et al., 2013; Hales et al., 2016). This evidence concerns the gene SNRNP70 and Alzheimer disease.