FUNCTIONAL DOMAINS ON CHEMICALLY-MODIFIED TAU-PROTEIN

1. Neurofibrillary tangles present in Alzheimer's disease and, in a lo wer proportion, in aged brains are formed mainly by paired helical fil aments. The microtuble-associated protein tau is a major structural co mponent of these filaments. In order to increase our understanding of the aberrant behaviour of tau protein leading to its assembly into pai red helical filaments, studies were carried out using chemical modific ations of brain tau protein. 2. Selective carbamoylation of tau with K CNO resulted in an irreversible modification of lysine residues on tau protein. The capacity of chemically modified tau protein to induce tu bulin assembly, under standard in vitro microtubule polymerization con ditions, decreased gradually in relation to the increase in concentrat ion of the modifying reagent. 3. Interestingly, carbamoylated tau prot ein exhibited the capacity to self-assemble into polymeric structures resembling those of paired helical filaments, after incubating the mod ified protein at concentrations higher than 1.0 mg/ml, at 37-degrees-C with KCNO. 4. The nature of polymers obtained from cabamoylated tau p rotein was analyzed by ultrastructural studies. The data provide new c lues toward our understanding of the anomalous interactions of tau in Alzheimer's disease.