title: The amyloid peptide of Alzheimer's disease is not produced by internal initiation of translation generating C-terminal amyloidogenic fragments of its precursor.
abstract: The molecular mechanisms of the amyloid peptide (A beta) production from the amyloid precursor protein (APP) remain unclear and it has been suggested that initiation of translation at methionine 596, which immediately precedes the A beta sequence, could generate soluble amyloidogenic fragments. We show that the amyloid peptide is actually produced by expression of the C-terminal 100 residues of the APP, using methionine 596 as an initiation codon. However, the amyloid peptide is no longer detectable when a stop codon is introduced in the APP mRNA, before the A beta coding region. These results strongly suggest that A beta is produced by degradation of APP and not by local translation of its mRNA.
authors.affiliation: Université Catholique de Louvain, Laboratoire de Neurochimie, UCL 1350, Brussels, Belgium.
authors.forename: A F
authors.initials: AF
authors.lastname: Macq
authors.forename: B
authors.initials: B
authors.lastname: Philippe
authors.forename: J N
authors.initials: JN
authors.lastname: Octave
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D018076:DNA, Complementary; D006801:Humans; D015151:Immunoblotting; D008715:Methionine
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D018076:DNA, Complementary; D008715:Methionine