title: Antibodies to amyloid beta protein (A beta) crossreact with glyceraldehyde-3-phosphate dehydrogenase (GAPDH).
abstract: In the present study, we characterized the epitope of a monoclonal antibody against purified amyloid plaque cores (Am-3). By immunocytochemical experiments, Am-3 stained cerebrovascular and senile plaque amyloid in brain sections of patients with Alzheimer's disease (AD) in a similar manner to that of antibodies against amyloid beta-protein (A beta). By Western blotting experiments, Am-3 recognized only a 35 kDa protein, 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 dot-binding assay. Therefore, we concluded that Am-3 recognized both GAPDH and native A beta. Other monoclonal antibodies (6C6 and AmT-1) against the synthetic peptide corresponding to residues 1-28 of A beta also 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 conformational epitopes. The possibility of crossreactions would complicate immunochemical and immunocytochemical studies of brain aging, AD and Down's syndrome. The implications of crossreactivity in developing immunological assays and in investigating the amyloid deposits of AD are discussed.
authors.affiliation: Department of Neurology, University of Tsukuba, Ibaraki, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Tamaoka
authors.forename: R
authors.initials: R
authors.lastname: Endoh
authors.forename: S
authors.initials: S
authors.lastname: Shoji
authors.forename: H
authors.initials: H
authors.lastname: Takahashi
authors.forename: K
authors.initials: K
authors.lastname: Hirokawa
authors.forename: D B
authors.initials: DB
authors.lastname: Teplow
authors.forename: D J
authors.initials: DJ
authors.lastname: Selkoe
authors.forename: H
authors.initials: H
authors.lastname: Mori
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D005260:Female; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged
chemical_list: D016564:Amyloid beta-Protein Precursor; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases