Biology of presenilins as causative molecules for Alzheimer disease.

Many missense mutations in the presenilins are associated with autosomal dominant forms of familial Alzheimer disease (AD). Presenilin genes encode polytopic transmembrane proteins, which are processed by proteolytic cleavage and form high-molecular-weight complexes under physiological conditions. The presenilins have been suggested to be functionally involved in developmental morphogenesis, apoptosis signal pathways, and processing of selected proteins including beta-amyloid precursor protein. Although the underlying mechanism in which presenilin mutations lead to development of AD remains elusive, one consistent mutational effect is an overproduction of long-tailed amyloid beta-peptides. Furthermore, presenilins interact with beta-catenin to form presenilin complexes and presenilin mutations effect beta-catenin signalling pathways.