[Presenilins as a marker of Alzheimer's disease]

Although the sporadic form of Alzheimer's disease is the most common, rare familial variants exist. Approximately 50% of these cases are caused by a mutation in the presenilin genes. Mutations in presinilin genes give rise to Alzheimer's disease in a dominant pattern of inheritance with an early age of onset (< 60 years). Both presenilins (PS-1 and PS-2) are transmembrane proteins localized in the intracellular membranes of the endoplasmatic reticulum and Golgi apparatus. This suggests they play a role in transport or sorting of proteins in the cell. Different lines of evidence directly link presenilin to the formation of beta-amyloid, an important constituent of senile plaques. PS-1 has an essential function during development: mice lacking intact PS-1 are not viable. In addition, structural and functional homologies have been identified between presenilins and Notch signal transduction pathways, which play a role in development. The discovery of the presenilin mutations has provided a new angle to Alzheimer's disease research. Eventually, this will probably greatly contribute to knowledge of the pathogenesis of the disease and in time support the development of novel therapeutic strategies.