Initiation and synergistic fibrillization of tau and alpha-synuclein |
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Authors: | Giasson Benoit I Forman Mark S Higuchi Makoto Golbe Lawrence I Graves Charles L Kotzbauer Paul T Trojanowski John Q Lee Virginia M-Y |
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Institution: | Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine. |
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Abstract: | Alpha-synuclein (alpha-syn) and tau polymerize into amyloid fibrils and form intraneuronal filamentous inclusions characteristic of neurodegenerative diseases. We demonstrate that alpha-syn induces fibrillization of tau and that coincubation of tau and alpha-syn synergistically promotes fibrillization of both proteins. The in vivo relevance of these findings is grounded in the co-occurrence of alpha-syn and tau filamentous amyloid inclusions in humans, in single transgenic mice that express A53T human alpha-syn in neurons, and in oligodendrocytes of bigenic mice that express wild-type human alpha-syn plus P301L mutant tau. This suggests that interactions between alpha-syn and tau can promote their fibrillization and drive the formation of pathological inclusions in human neurodegenerative diseases. |
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