Alternative splicing in a presenilin 2 variant associated with Alzheimer disease

Abstract

These data suggest that PSEN2 K115Efs*11 is a likely pathogenic variant associated with AD. We uncovered novel <i>PSEN2</i> alternative transcripts in addition to previously reported <i>PSEN2</i> splice isoforms associated with sporadic AD. In the context of a frameshift, these alternative transcripts return to the canonical reading frame with potential to generate deleterious protein products. Our findings suggest novel potential mechanisms by which <i>PSEN</i> variants may influence AD pathogenesis, highlighting the complexity underlying genetic contribution to disease risk.