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 Aβ42 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 Aβ, particularly Aβ42, in Alzheimer's disease. These data provide strong evidence that alterations in Aβ concentration are an early and critical event in the pathology of Alzheimer's disease.
Eckman, C. B. (1998). Presenilins and alzheimer’s disease: The role of Aβ42. Journal of Neural Transmission, Supplement, (53), 181–184. https://doi.org/10.1007/978-3-7091-6467-9_16