Polymerization of tau peptides into fibrillar structures. The effect of FTDP-17 mutations

The peptides corresponding to the four repeats found in the microtubule bin ding region of tau protein were synthesized and their ability for self-aggr egation in presence of heparin or chondroitin sulfate was measured. Mainly, only the peptide containing the third tau repeat is able to form polymers in a high proportion. Additionally, the peptide containing the second repea t aggregates with a very low efficiency, However, when this peptide contain s the mutation (P301L), described in a fronto temporal dementia, it is able to form polymers at a higher extent. Finally, it is suggested to have a ro le for the first and fourth tau repeats. It could be to decrease the abilit y of the third tau repeat for self-aggregation in the presence of heparin, (C) 1999 Federation of European Biochemical Societies.