The low-density lipoprotein receptor-related protein 6 (LRP6) gene on chromosome 12 is expressed as a co-receptor for Wnt signaling. Defects in Wnt signaling have been validated as risk factors for neurodegenerative disorders such as schizophrenia, autism, and AD. Wnt signaling proteins, such as beta-catenin or glycogen synthase kinase 3 beta, can form complexes with presenilins, which suggests they might play an important role in Abeta processing and neurotoxicity. Genetic linkage studies have suggested an association between LOAD and chromosome 12. Polymorphisms in LRP6 might result in abnormalities in plasma ApoE catabolism and in Wnt signaling.163
