title: [Presenilins as a marker of Alzheimer's disease].
abstract: 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.
authors.affiliation: Academisch Medisch Centrum, afd. Neurologie, Amsterdam.
authors.forename: W
authors.initials: W
authors.lastname: Scheper
authors.forename: W A
authors.initials: WA
authors.lastname: van Gool
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000096:biosynthesis; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000648:ultrastructure; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004721:Endoplasmic Reticulum / Q000648:ultrastructure; D005819:Genetic Markers / Q000235:genetics; D006056:Golgi Apparatus / Q000648:ultrastructure; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics*; D051379:Mice; D017354:Point Mutation; D053764:Presenilin-1; D053766:Presenilin-2
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D005819:Genetic Markers; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2