Presenilins and Alzheimer's disease: the role of A beta 42.
The presenilin proteins, localized predominantly to the endoplasmic reticulum, are multi-transmembrane spanning proteins that are processed to form an approximately 27 kD N-terminal fragment and a corresponding 19 kD C-terminal fragment. Mutations in the presenilin 1 and presenilin 2 genes have been identified that cause early onset familial Alzheimer's disease. Analysis of plasma and fibroblasts from patients revealed that these mutations increase the concentration of A beta 42. Cells and transgenic animals containing these mutations both give rise to increases in the extracellular concentration of this peptide providing further evidence for the role of A beta, particularly A beta 42, in Alzheimer's disease. These data provide strong evidence that alterations in A beta concentration are an early and critical event in the pathology of Alzheimer's disease.
Eckman
C B
CB
Mayo Clinic, Jacksonville, Fl., USA.
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000235:genetics; D053764:Presenilin-1; D053766:Presenilin-2
D016229:Amyloid beta-Peptides; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; D053766:Presenilin-2; C075222:amyloid beta-protein (1-42)