Homology-based cappers for blocking tau aggregation and identifying disease-specific tau filaments

Abstract

A polypeptide capable of inhibiting Tau aggregation includes an amino acid sequence sharing between 20% and 99% sequence similarity with a structured core region of a pathological Tau filament, where the polypeptide is capable of binding to an end of a Tau fibril and reducing Tau aggregation or Tau seeding activity. The polypeptide may include an amino acid sequence derived from a microtubule-associated protein such as MAP2 or MAP4. Methods for inhibiting Tau aggregation in a biological sample include contacting the biological sample containing Tau with the polypeptide, where the polypeptide binds to an end of a Tau fibril and reduces Tau aggregation relative to a control sample.

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