PSEN1 and familial Alzheimer disease: Indeed, the accumulation of misfolded protein in ER caused by gene mutations is most likely the central event in the initiation of cell death in some diseases including autosomal-dominant diabetes and familial Alzheimer's disease-linked presenilin-1 (PS1) and the alternatively spliced form of the presenilin-2 gene lacking exon 5 (PS2V)-induced cell apoptosis by effect on ER stress response [27-31].