Characterization of amyloid fibril beta-peptide in familial Alzheimer's disease with APP717 mutations.
Amyloid fibrils were isolated from the brain tissue of two individuals who died with familial Alzheimer's disease, one with the phenylalanine 717 mutation in amyloid precursor protein (APP) and one with the isoleucine 717 APP mutation. After solubilization in guanidine hydrochloride and fractionation by sieve chromatography, low molecular weight fractions were treated with cyanogen bromide to generate the beta-peptide fragment starting after the methionine at position 35. Amino acid sequence analysis of all resultant peptides identified the peptide Val-Gly-Gly-Val-Val-Ile-Ala which represents residues 36-42 of the beta-amyloid peptide. No sequence beyond position 42 was found. These findings show that the amino acid substitution at position 717 is not incorporated into the amyloid deposits and suggests that the mutation may have metabolic affects which determine pathogenesis.
Liepnieks
J J
JJ
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202-5120.
Ghetti
B
B
Farlow
M
M
Roses
A D
AD
Benson
M D
MD
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002540:Cerebral Cortex / Q000473:pathology; D003488:Cyanogen Bromide; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification; D017354:Point Mutation
C094559:APP717; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D003488:Cyanogen Bromide