for 42 genes (FDR < 0.05), of which 11 genes overlap with the Alzheimer’s disease-associated splicing in the cortex including APP, PICALM, and NDRG2 (Fig. 2d; Supplementary Table 9). Despite the small sample size, these in vitro data suggest that tau accumulation in neurons – at a stage in which neurons are accumulating phospho-tau but are not apoptotic – may be sufficient to induce some of the splicing alterations that we observed in cortical tissue of human subjects; this in vitro validation of disease-related splicing changes suggests that this Alzheimer’s disease-altered splicing (1) is unlikely to be related to confounding factors from autopsy or the agonal state and (2) has specific target RNAs that can be modeled in vitro.
