Secretory cleavage site of Alzheimer amyloid precursor protein is heterogeneous in Down's syndrome brain.
A beta (beta/A4) is the major constituent of brain amyloid in Alzheimer's disease (AD), Down's syndrome (DS) and normal aged persons. This protein is presumably derived by normal proteolysis from a precursor protein (APP). In this study, C-terminal fragments of APP in a Tris/Triton soluble fraction were partially purified from DS brain by heparin-affinity and reverse phase chromatography, and analyzed by N-terminal amino acid sequencing after SDS polyacrylamide gel electrophoresis and Western blotting. We found at least six different C-terminal fragments including those with the entire A beta region. These results suggest that secretory processing of APP is heterogeneous and generates amyloidogenic C-terminal fragments.
Kametani
F
F
Department of Molecular Biology, Tokyo Institute of Psychiatry, Japan.
Tanaka
K
K
Tokuda
T
T
Ikeda
S
S
D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D004314:Down Syndrome / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D017421:Sequence Analysis
D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments