Direct association of presenilin‐1 with β‐catenin

Abstract
Families bearing mutations in the presenilin-1 (PS1) gene develop Alzheimer's disease (AD). However, the mechanism through which PS1 causes AD is unclear. The co-immunoprecipitation with PS1 in transfected COS-7 cells indicates that PS1 directly interacts with endogenous β-catenin, and the interaction requires residues 322–450 of PS1 and 445–676 of β-catenin. Both proteins are co-localized in the endoplasmic reticulum. Over-expression of PS1 reduces the level of cytoplasmic β-catenin, and inhibits β-catenin-T cell factor-regulated transcription. These results indicate that PS1 plays a role as inhibitor of the β-catenin signal, which may be connected with the AD dysfunction