Some of these effects of Alzheimer’s disease variants on splicing are known, such as the 8-fold increase in full-length CD33 isoform16,32, but several of these - in CLU, PICALM, and PTK2B - have not been previously reported (Supplementary Table 10). These results delineate the initial events along the cascade of functional consequences for these three Alzheimer’s disease variants and provide important mechanistic insights into their development as potential therapeutic targets.
