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 language||English (US)|
|Number of pages||7|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Dec 15 1993|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology