The immunohistochemical demonstration of subsequences of the precursor of the amyloid A4 protein in senile plaques in Alzheimer's disease.
The actual presence of the predicted precursor of Alzheimer's disease amyloid A4 protein, reported by Kang et al. (1987) in the Alzheimer brain, has yet to be verified. To identify the various regions of this precursor, antibodies were raised against three synthetic polypeptides, R35 (residues 274-286), R36 (residues 527-540), and R37 (residues 681-695), subsequences of the precursor protein; the specificity of these antibodies was ascertained by ELISA. Upon immunohistochemical examination, the antibody to R35 failed to react, but the antibody to R36 (the extracellular part) stained the amyloid of senile plaques and the staining pattern was identical to that of anti-A4 antibody. The antibody to R37 (the C-terminal intracellular part) stained what may be degenerating neurites in senile plaques whereas the amyloid remained unstained. An anti-neurofilament (NF) antibody reacted with some of the R37-positive grains, but R37-negative grains also were seen. Further, some R37-positive grains were not stained by the anti-NF antibody. The anti-GFAP antibody and the anti-macrophage antibody did not stain the R37-positive grains. These findings indicate that the amyloid protein in senile plaques actually contains a larger polypeptide than the A4 protein, and suggest that the intracellular C-terminal part of the precursor may exist in the degenerated neurites seen in senile plaques.
Ishii
T
T
Laboratory of Molecular Biology, Psychiatric Research Institute of Tokyo, Japan.
Kametani
F
F
Haga
S
S
Sato
M
M
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D000682:Amyloid / Q000032:analysis*; D016229:Amyloid beta-Peptides; D003599:Cytoskeleton / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007382:Intermediate Filaments / Q000032:analysis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011498:Protein Precursors / Q000378:metabolism*
D000682:Amyloid; D016229:Amyloid beta-Peptides; D011498:Protein Precursors