Aberrant proteolysis of the beta-amyloid precursor protein in familial Alzheimer's disease lymphoblastoid cells.
Lymphoblastoid cells from patients with early-onset and late-onset familial Alzheimer's disease showed increased expressions of beta-amyloid precursor mRNA and protein as well as interleukin-1 and alpha 1-antichymotrypsin protein. Early-onset and late-onset familial Alzheimer's disease cells had greater production of 16-kDa beta-amyloid C-terminal preamyloid peptides than did normal cells. A pulse-chase experiment indicated that aberrant processing of this peptide resulted in its abnormal accumulation. Furthermore, the peptide prepared from early-onset familial Alzheimer's disease cells using formic acid could be separated into four discrete fragments. The N-terminal amino acid sequencing of each fragment indicated that the 16-kDa peptide was generated by cleavage, principally at the 30 amino acids N-terminal to beta-amyloid. Both the enhanced synthesis and aberrant processing of the beta-amyloid precursor protein, therefore, are basic processes associated with familial Alzheimer's disease lymphoblastoid cells.
Matsumoto
A
A
Department of Radiation Biophysics and Genetics, Kobe University School of Medicine, Japan.
Fujiwara
Y
Y
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D004854:Herpesvirus 4, Human; D006801:Humans; D007163:Immunosorbent Techniques; D007700:Kinetics; D008214:Lymphocytes / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D012333:RNA, Messenger