Initiation and synergistic fibrillization of tau and alpha-synuctein

Benoit I. Giasson, Mark S. Forman, Makoto Higuchi, Lawrence I. Golbe, Charles L. Graves, Paul T. Kotzbauer, John Q. Trojanowski, Virginia M.Y. Lee

Research output: Contribution to journalArticlepeer-review

632 Scopus citations

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 fibrilization 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.

Original languageEnglish (US)
Pages (from-to)636-640
Number of pages5
JournalScience
Volume300
Issue number5619
DOIs
StatePublished - Apr 25 2003

All Science Journal Classification (ASJC) codes

  • General

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