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Science 25 April 2003:
Vol. 300. no. 5619, pp. 636 - 640
DOI: 10.1126/science.1082324
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Reports

Initiation and Synergistic Fibrillization of Tau and Alpha-Synuclein

Benoit I. Giasson,1 Mark S. Forman,1 Makoto Higuchi,1 Lawrence I. Golbe,3 Charles L. Graves,1 Paul T. Kotzbauer,1 John Q. Trojanowski,1,2 Virginia M.-Y. Lee1,2*

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.

1 Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine
2 Institute on Aging, University of Pennsylvania School of Medicine, 3600 Spruce Street, Philadelphia, PA 19104, USA.
3 Department of Neurology, University of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.

* To whom correspondence should be addressed. E-mail: vmylee{at}mail.med.upenn.edu

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