Murray, M.M., C.J. Jones, and R.F. Clark. 2000. "The presenilin gene is very highly conserved throughout evolution." Neurobiology of Aging 21(supplement 1):S48.

Mutations in the presenilin-1 and -2 genes have been linked to the majority of cases of familial early-onset Alzheimer's disease. These genes appear to encode for integral membrane proteins with six to eight transmembrane domains and localized primarily to the endoplasmic reticulum and Golgi bodies. It has been demonstrated that presenilins play a role in normal development in the fly, nematode, and mouse. Alzheimer disease-causing mutations in the presenilin genes alter the proteolysis of amyloid precursor protein in humans, potentially leading to increased amyloid plaque production. To learn which regions of the presenilin protein are likely to be the most important for the function of the molecule, we undertook a study to find the most highly conserved regions of the gene throughout evolution. Exploiting the high degree of conservation of the presenilin genes in vertebrates, the fruit fly, and the nematode, we isolated and cloned the homologous gene from the plant Arabidopsis thaliana. The Arabidopsis presenilin (APS) shows considerable homology to that of animal presenilins, with large regions displaying 50% homology. In fact, there is one 15 amino acid motif that is 100% identical in all the presenilins characterized thus far. Using the program PHYLIP, evolutionary trees have been constructed that indicate the evolutionary history of the presenilin gene. These experiments will facilitate our comprehension of the function and structure of the presenilin gene and its role in development and Alzheimer's disease pathogenesis.