Immunoreactivity of an antibody to a beta/A4 sequence with Alzheimer paired helical filaments and tau protein.
beta/A4, a peptide that forms the extracellular amyloid fibrils of Alzheimer senile plaques, has also been proposed to be a component of Alzheimer paired helical filaments (PHFs). We compared BR88, an antiserum to amino acids 1-12 of beta/A4, with BR126, an antiserum to the sequence SEKLDFKDRVQS in tau protein, since tau protein is the only confirmed component of PHFs. In enzyme-linked immunosorbent assays (ELISAs), both antibodies reacted with pronase-treated PHFs better after PHFs were treated with guanidine. tau protein shares no sequence homology with beta/A4. Nevertheless, BR88 cross-reacted with human recombinant tau isoforms by ELISA and Western blot analysis with potencies comparable to those for anti-tau antibodies. BR88 reacted with a beta/A4 peptide as well on a molar basis as with tau protein and showed some reactivity to the tubulin-binding region of tau protein. In conclusion, the beta/A4 antiserum BR88 cross-reacts with tau protein, possibly explaining its reactivity with PHFs.
Pharmacology Department, ICI Pharmaceuticals Group, Wilmington, DE 19897.
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Caputo
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Scott
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Brunner
D000368:Aged; D000544:Alzheimer Disease / Q000276:immunology*; D016564:Amyloid beta-Protein Precursor / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007106:Immune Sera / Q000276:immunology*; D016874:Neurofibrillary Tangles / Q000276:immunology*; D016875:tau Proteins / Q000276:immunology*
D016564:Amyloid beta-Protein Precursor; D007106:Immune Sera; D016875:tau Proteins