The β-amyloid peptide is a major component of the characteristic pathologic deposits found in the brains of Alzheimer's disease patients (lkeda et al.. 1989). Based on the amino acid sequence of this peptide. cDNA clones encoding a much larger
precursor protein were isolated (Goldgaber et al., 1987 ; Kange et al., 1987 ; Robakis et al., 1987 ; Tanzi et al., 1987 a ; Shivers et al., 1988 ; Zain et al., 1988). Subsequently, cDNA clones encoding alternative forms of this β-amyloid
precursor
protein (BAPP) were found (Kitaguchi et al., 1988 ; Ponte et al., 1988 ; Tanzi et al., 1988). All the cDNA clones isolated so far include the β-amyloid peptide sequence. Comparison of cDNA and genomic clones for BAPP indicate that the various
forms of
mRNA are the products of alternative splicing of a gene that has at least 18 exons (Lemaire et al., 1989). the predioted protein precursors translated from these mRNAs are 695, 751, or 770- amino acids in length.
The presence of a 56-amino acid insert with high homology to a Kunitz-type protease inhibitor distinguishes the BAPP-770/751 precursor from BAPP-695 (Kitaguchi et al., 1988 ; Ponte et al., inhibitor, protease nexin-II (Oltersdort et al., 1989).
The
presence of another protease inhibitor, α1-antichymotrypsin, in Alzheimer's disease-specific deposits also is now established (A braham et al., 1988). Such findings have stimulated conjecture that proteolytic processing or other
posttranslational
mechanisms may play a rle in the etiology of Alzhermer's disease (see Carrell, 1988 and Abraham and poter, 1989 for reviews).
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