Presenilines en de ziekte van Alzheimer

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 β-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.