Another more in-depth label-free analysis of the brain insoluble proteome was performed, identifying 4216 proteins with 36 differentially expressed proteins (DEPs) in AD, including Aβ, tau, APOE, complement components, and some novel components of RNA splicing dysfunction, such as U1 small nuclear ribonucleoprotein (snRNP) (21). This evidence concerns the gene APOE and Alzheimer disease.