Characterization of Amyloid Familial β-Peptide in Familial Alzheimer′s Disease with APP717 Mutations

J. J. Liepnieks, Bernardino Ghetti, Martin Farlow, A. D. Roses, Merrill Benson

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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 β-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 β-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.

Original languageEnglish
Pages (from-to)386-392
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume197
Issue number2
DOIs
StatePublished - Dec 15 1993

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Amyloid
Alzheimer Disease
Amyloid beta-Protein Precursor
Peptides
Mutation
Amino Acids
Cyanogen Bromide
Peptide Fragments
Sieves
Isoleucine
Guanidine
Protein Sequence Analysis
Amyloid Plaques
Amino Acid Substitution
Fractionation
Chromatography
Phenylalanine
Methionine
Brain
Substitution reactions

ASJC Scopus subject areas

  • Molecular Biology
  • Biophysics
  • Biochemistry

Cite this

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abstract = "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 β-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 β-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.",
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AU - Roses, A. D.

AU - Benson, Merrill

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