Initiation and Synergistic Fibrillization of Tau and Alpha-Synuclein

Abstract

Alpha-synuclein (α-syn) and tau polymerize into amyloid fibrils and form intraneuronal filamentous inclusions characteristic of neurodegenerative diseases. We demonstrate that α-syn induces fibrillization of tau and that coincubation of tau and α-syn synergistically promotes fibrillization of both proteins. The in vivo relevance of these findings is grounded in the co-occurrence of α-syn and tau filamentous amyloid inclusions in humans, in single transgenic mice that express A53T human α-syn in neurons, and in oligodendrocytes of bigenic mice that express wild-type human α-syn plus P301L mutant tau. This suggests that interactions between α-syn and tau can promote their fibrillization and drive the formation of pathological inclusions in human neurodegenerative diseases.