Distinct α-synuclein strains differentially promote tau inclusions in neurons.
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| Abstract |
Many neurodegenerative diseases are characterized by the accumulation of insoluble protein aggregates, including neurofibrillary tangles comprised of tau in Alzheimer's disease and Lewy bodies composed of α-synuclein in Parkinson's disease. Moreover, different pathological proteins frequently codeposit in disease brains. To test whether aggregated α-synuclein can directly cross-seed tau fibrillization, we administered preformed α-synuclein fibrils assembled from recombinant protein to primary neurons and transgenic mice. Remarkably, we discovered two distinct strains of synthetic α-synuclein fibrils that demonstrated striking differences in the efficiency of cross-seeding tau aggregation, both in neuron cultures and in vivo. Proteinase K digestion revealed conformational differences between the two synthetic α-synuclein strains and also between sarkosyl-insoluble α-synuclein extracted from two subgroups of Parkinson's disease brains. We speculate that distinct strains of pathological α-synuclein likely exist in neurodegenerative disease brains and may underlie the tremendous heterogeneity of synucleinopathies.
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| Authors | Jing L Guo, Dustin J Covell, Joshua P Daniels, Michiyo Iba, Anna Stieber, Bin Zhang, Dawn M Riddle, Linda K Kwong, Yan Xu, John Q Trojanowski, Virginia M Y Lee |
| Journal | Cell (Cell) Vol. 154 Issue 1 Pg. 103-17 (Jul 03 2013) ISSN: 1097-4172 [Electronic] United States |
| PMID | 23827677 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2013 Elsevier Inc. All rights reserved. |
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