Presenilins and Alzheimer's disease:: the role of Aβ42

The presenilin proteins, localized predominantly to the endoplasmic reticulum, are multi-transmembrane spanning proteins that are processed to form an approximately 27kD N-terminal fragment and a corresponding 19kD C-terminal fragment. Mutations in the presenilin 1 and presenilin 2 genes have been identified that cause early onset familial Alzheimer's disease Analysis of plasma and fibroblasts from patients revealed that these mutations increase the concentration of A beta 42 Cells and transgenic animals containing these mutations both give rise to increases in the extracellular concentration of this peptide providing further evidence for the role of A beta, particularly A beta 42, in Alzheimer's disease. These data provide strong evidence that alterations in A beta concentration are an early and critical event in the pathology of Alzheimer's disease.