ANTIBODIES TO AMYLOID-BETA PROTEIN (A-BETA) CROSS-REACT WITH GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE (GAPDH)

In the present study, we characterized the epitope of a monoclonal ant ibody against purified amyloid plaque cores (Am-3). By immunocytochemi cal experiments, Am-3 stained cerebrovascular and senile plaque amyloi d in brain sections of patients with Alzheimer's disease (AD) in a sim ilar manner to that of antibodies against amyloid beta-protein (A beta ). By Western blotting experiments, Am-3 recognized only a 35 kDa prot ein, which was revealed to be glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and not A beta or beta amyloid precursor protein (beta PP). However, Am-3 recognized both GAPDH and purified native A beta in a do t-binding assay. Therefore, we concluded that Am-3 recognized both GAP DH and native A beta. Other monoclonal antibodies (6C6 and AmT-1) agai nst the synthetic peptide corresponding to residues 1-28 of A beta als o recognized these proteins. Because the amino acid sequences of these two proteins are not homologous, we propose that the crossreactivity between A beta and GAPDH is a consequence of their similar conformatio nal epitopes. The possibility of crossreactions would complicate immun ochemical and immunocytochemical studies of brain aging, AD and Down's syndrome. The implications of crossreactivity in developing immunolog ical assays and in investigating the amyloid deposits of AD are discus sed.