Aberrant proteolysis of the β‐amyloid precursor protein in familial Alzheimer's disease lymphoblastoid cells

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Abstract
Lymphoblastoid cells from patients with early‐onset and late‐onset familial Alzheimer's disease showed increased expressions of β‐amyloid precursor mRNA and protein as well as interleukin‐1 and α1‐antichymotrypsin protein. Early‐onset and late‐onset familial Alzheimer's disease cells had greater production of 16‐kDa β‐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 β‐amyloid. Both the enhanced synthesis and aberrant processing of the β‐amyloid precursor protein, therefore, are basic processes associated with familial Alzheimer's disease lymphoblastoid cells.