RNA STIMULATES AGGREGATION OF MICROTUBULE-ASSOCIATED PROTEIN-TAU INTOALZHEIMER-LIKE PAIRED HELICAL FILAMENTS

The microtubule-associated protein tau is the main component of the pa ired helical filaments (PHFs) of Alzheimer's disease, the most common senile dementia, To understand the origin of tau's abnormal assembly m e have studied the influence of other cytosolic components, Here me re port that PHF assembly is strongly enhanced by RNA. The RNA-induced as sembly of PHFs is dependent on the formation of intermolecular disulfi de bridges involving Cys(322) in the third repeat of tau, and it inclu des the dimerization of tau as an early intermediate, Three-repeat con structs polymerize most efficiently, two repeat constructs are the min imum number required for assembly, and even all six full-length isofor ms of tau can be induced to form PHFs by RNA.