POLYMERIZATION OF MICROTUBULE-ASSOCIATED PROTEIN-TAU UNDER NEAR-PHYSIOLOGICAL CONDITIONS

Neurofibrillary tangles, which form in certain degenerating neurons in the brains of patients with Alzheimer's disease, are amassed from fil aments having a straight or paired helical morphology. Solubilization of these filaments reveals that they are composed of the microtubule-a ssociated protein tau. It has not previously been shown, however, that tan win assemble to form filaments of similar morphology under condit ions representative of the intracellular environment. We have succeede d in forming such filaments using tau purified from porcine or rat mic rotubules. The filaments are relatively straight with narrowing at irr egular intervals, and are about 10 nn wide, a morphology similar to th at of straight filaments seen in Alzheimer's disease neurofibrillary t angles. At tau concentrations of 1-10 mu M, in vitro assembly occurs a t physiological pH, ionic strength, temperature, and reducing potentia l, and each one of these factors modulates the reaction, Assembly is j udged to be only slowly reversible by the exponential rather than norm al distribution of filament lengths, and by the limited disassembly ob served under conditions which inhibit polymerization. Tau purified dir ectly from whole brain tissue rather than from microtubules does not p olymerize under conditions described in this report.