title: Increased Abeta42(43) from cell lines expressing presenilin 1 mutations.
abstract: Mutations in the presenilin 1 (PS1) gene on chromosome 14 are a major cause of autosomal dominant, early-onset Alzheimer's disease. Here, we show that transfecting cells with several mutant, but not wild-type, PS1 cDNAs alters the processing of the amyloid precursor protein (APP) such that more Abeta42(43) is produced, confirming and extending several recent reports. The most effective mutation in this regard was the exon 9 splice-out mutation (delta9). The correlation between the size of the effect on APP processing and the age of onset of disease assessed in families with the mutations was not informative, and the possible reasons for this are discussed.
authors.affiliation: Mayo Clinic Jacksonville, FL 32224, USA.
authors.forename: N D
authors.initials: ND
authors.lastname: Mehta
authors.forename: L M
authors.initials: LM
authors.lastname: Refolo
authors.forename: C
authors.initials: C
authors.lastname: Eckman
authors.forename: S
authors.initials: S
authors.lastname: Sanders
authors.forename: D
authors.initials: D
authors.lastname: Yager
authors.forename: J
authors.initials: J
authors.lastname: Perez-Tur
authors.forename: S
authors.initials: S
authors.lastname: Younkin
authors.forename: K
authors.initials: K
authors.lastname: Duff
authors.forename: J
authors.initials: J
authors.lastname: Hardy
authors.forename: M
authors.initials: M
authors.lastname: Hutton
mesh_terms: D017668:Age of Onset; D000544:Alzheimer Disease / Q000235:genetics; D000704:Analysis of Variance; D015153:Blotting, Western; D002460:Cell Line; D002883:Chromosomes, Human, Pair 14; D002999:Clone Cells; D018076:DNA, Complementary / Q000032:analysis; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney / Q000196:embryology; D008565:Membrane Proteins / Q000235:genetics*; D017354:Point Mutation; D053764:Presenilin-1; D014162:Transfection
chemical_list: D018076:DNA, Complementary; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1