Recently, the involvement of ER stress in various diseases, such as diabetes, cancer, and ischemic cardiac disease, has been reported.27, 28, 29 With regard to neurodegenerative diseases, a series of reports have described the involvement of ER stress in Alzheimer's disease,28, 29 Parkinson's disease,30 and polyglutamine diseases.19 We have described the relationship between presenilin 1 and ER stress.31, 32 Given these findings, drugs that suppress ER stress may be valuable new targets in the treatment of these diseases. Here, PSEN1 is linked to early-onset autosomal dominant Alzheimer disease.