BOVINE AND HUMAN TAU, HIGHLY HOMOLOGOUS BUT LESS CROSS-REACTIVE - IMPLICATIONS FOR ALZHEIMER-DISEASE

Tau is a highly conserved protein during evolution. However, polymerization of tau into paired helical filaments, a characteristic of Alzheimer disease is unique to humans and has not been seen in animals. The cause of this phenomenon is not known. The cDNA-derived amino acid sequences of bovine and human tau are highly homologous. In this study we show that despite the high homology there are marked differences between the immunoreactivities of human and bovine tau. The four antibodies employed in this study were the monoclonal Tau-1 to the bovine protein, two polyclonal anti-bovine tau 92e and 111e and a polyclonal anti-human tau 113e. The monoclonal antibody Tau-1, the epitope of which lies in the amino acid residues 196-215 of bovine tau and residues 189-207 of human tau differing by a single amino acid, a glycine at position 196 in bovine protein with a proline at position 189 in human protein, reacts 2.3 +/- 0.5 times better with bovine tau than with human tau. Both polyclonal antibodies against bovine tau, 92e and 111e react 25 +/- 7 and 45 +/- 17 fords, respectively, better with bovine tau than human tau, whereas the polyclonal antibody 113e to a human tau peptide does not cross-react with bovine tau. The differences in cross-reactivity that are probably due to differences in conformation of tau from the two species were found using both cytosolic extracts and tau isolated from human and bovine brains. Conformational differences such as those observed between human and bovine taus might play a role in the formation of PHF in human and not in animals.