title: Novel Leu723Pro amyloid precursor protein mutation increases amyloid beta42(43) peptide levels and induces apoptosis.
abstract: A novel missense mutation, Leu723Pro, in the amyloid precursor protein (APP) gene was discovered in an early-onset Alzheimer's disease family. Expression of L723P mutant APP complementary DNA in CHO cells resulted in a 1.4- to 1.9-fold increased production of the 42(43)-amino acid length amyloid beta peptide compared with the wild-type sequence and was capable of causing apoptosis. The mutation is predicted to alter the luminal transmembrane length and helical arrangement of the APP molecule and thus affect the gamma-secretase cleavage site.
authors.affiliation: Garvan Institute of Medical Research, Sydney, NSW, Australia.
authors.forename: J B
authors.initials: JB
authors.lastname: Kwok
authors.forename: Q X
authors.initials: QX
authors.lastname: Li
authors.forename: M
authors.initials: M
authors.lastname: Hallupp
authors.forename: S
authors.initials: S
authors.lastname: Whyte
authors.forename: D
authors.initials: D
authors.lastname: Ames
authors.forename: K
authors.initials: K
authors.lastname: Beyreuther
authors.forename: C L
authors.initials: CL
authors.lastname: Masters
authors.forename: P R
authors.initials: PR
authors.lastname: Schofield
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence / Q000235:genetics; D016466:CHO Cells / Q000378:metabolism; D006224:Cricetinae; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000502:physiology*; D010375:Pedigree; D010446:Peptide Fragments / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C098994:amyloid beta-protein (1-43)