title: Absence of mutation in the beta-amyloid cDNAs cloned from the brains of three patients with sporadic Alzheimer's disease.
abstract: Using an oligonucleotide probe, we isolated cDNA clones corresponding to the precursor of the beta-amyloid peptide (BAP) from brain libraries of 3 patients with sporadic Alzheimer's disease (AD). DNA sequencing showed that the largest cDNA clone encompasses 83% of the open reading frame proposed by Kang et al. to encode the BAP precursor (APP). cDNA clones from each of the 3 AD brain libraries were identical to the sequence of the APP-cDNAs cloned from normal adult human and fetal brain. An antisense-radiolabeled RNA copy of one of the AD clones detected a pattern of 3 gene transcripts measuring 3.5, 3.2 and 1.6 kilobases (kb) in both normal and AD brain RNAs. These data suggest that there are no mutations in or about the 42 amino acid (aa) sequence of BAP and that the accumulation of amyloid consistently found in AD may result from altered post-translational processing of APP.
authors.affiliation: Central Nervous System Biological Research Division, American Cyanamid Company, Pearl River, NY 10965.
authors.forename: M P
authors.initials: MP
authors.lastname: Vitek
authors.forename: C G
authors.initials: CG
authors.lastname: Rasool
authors.forename: F
authors.initials: F
authors.lastname: de Sauvage
authors.forename: S M
authors.initials: SM
authors.lastname: Vitek
authors.forename: R T
authors.initials: RT
authors.lastname: Bartus
authors.forename: B
authors.initials: B
authors.lastname: Beer
authors.forename: R A
authors.initials: RA
authors.lastname: Ashton
authors.forename: A F
authors.initials: AF
authors.lastname: Macq
authors.forename: J M
authors.initials: JM
authors.lastname: Maloteaux
authors.forename: A J
authors.initials: AJ
authors.lastname: Blume
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000682:Amyloid / Q000235:genetics*; D016229:Amyloid beta-Peptides; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics*; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes; D012016:Reference Values
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D015345:Oligonucleotide Probes; D004247:DNA