Amplification of Tau Fibrils from Minute Quantities of Seeds

Overview

Journal Biochemistry

Specialty Biochemistry

Date 2014 Aug 26

PMID 25153692

Citations 28

Authors

Virginia Meyer

Paul D Dinkel

Emily Rickman Hager

Martin Margittai

Affiliations

Soon will be listed here.

Abstract

The propagation of Tau pathology in Alzheimer's disease (AD) is thought to proceed through templated conversion of Tau protein into fibrils and cell-to-cell transfer of elongation-competent seeds. To investigate the efficiency of Tau conversion, we adapted the protein misfolding cyclic amplification assay used for the conversion of prions. Utilizing heparin as a cofactor and employing repetitive cycles of shearing and growth, synthetic Tau fibrils and Tau fibrils in AD brain extract are progressively amplified. Concurrently, self-nucleation is suppressed. The results highlight breakage-induced replication of Tau fibrils as a potential facilitator of disease spread.

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References

Kuret J, Congdon E, Li G, Yin H, Yu X, Zhong Q . Evaluating triggers and enhancers of tau fibrillization. Microsc Res Tech. 2005; 67(3-4):141-55. DOI: 10.1002/jemt.20187. View

Saborio G, Permanne B, Soto C . Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature. 2001; 411(6839):810-3. DOI: 10.1038/35081095. View

Wischik C, Novak M, Thogersen H, Edwards P, Runswick M, Jakes R . Isolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer disease. Proc Natl Acad Sci U S A. 1988; 85(12):4506-10. PMC: 280459. DOI: 10.1073/pnas.85.12.4506. View

Novak M, Kabat J, Wischik C . Molecular characterization of the minimal protease resistant tau unit of the Alzheimer's disease paired helical filament. EMBO J. 1993; 12(1):365-70. PMC: 413214. DOI: 10.1002/j.1460-2075.1993.tb05665.x. View

Siddiqua A, Luo Y, Meyer V, Swanson M, Yu X, Wei G . Conformational basis for asymmetric seeding barrier in filaments of three- and four-repeat tau. J Am Chem Soc. 2012; 134(24):10271-8. PMC: 3381011. DOI: 10.1021/ja303498q. View

Ramachandran G, Udgaonkar J . Evidence for the existence of a secondary pathway for fibril growth during the aggregation of tau. J Mol Biol. 2012; 421(2-3):296-314. DOI: 10.1016/j.jmb.2012.01.007. View

Ferrone F . Analysis of protein aggregation kinetics. Methods Enzymol. 1999; 309:256-74. DOI: 10.1016/s0076-6879(99)09019-9. View

Deleault N, Harris B, Rees J, Supattapone S . Formation of native prions from minimal components in vitro. Proc Natl Acad Sci U S A. 2007; 104(23):9741-6. PMC: 1887554. DOI: 10.1073/pnas.0702662104. View

Wischik C, Novak M, Edwards P, Klug A, Tichelaar W, Crowther R . Structural characterization of the core of the paired helical filament of Alzheimer disease. Proc Natl Acad Sci U S A. 1988; 85(13):4884-8. PMC: 280541. DOI: 10.1073/pnas.85.13.4884. View

10.

Legname G, Nguyen H, Peretz D, Cohen F, DeArmond S, Prusiner S . Continuum of prion protein structures enciphers a multitude of prion isolate-specified phenotypes. Proc Natl Acad Sci U S A. 2006; 103(50):19105-10. PMC: 1748184. DOI: 10.1073/pnas.0608970103. View

11.

Cohen S, Linse S, Luheshi L, Hellstrand E, White D, Rajah L . Proliferation of amyloid-β42 aggregates occurs through a secondary nucleation mechanism. Proc Natl Acad Sci U S A. 2013; 110(24):9758-63. PMC: 3683769. DOI: 10.1073/pnas.1218402110. View

12.

Siddiqua A, Margittai M . Three- and four-repeat Tau coassemble into heterogeneous filaments: an implication for Alzheimer disease. J Biol Chem. 2010; 285(48):37920-6. PMC: 2988394. DOI: 10.1074/jbc.M110.185728. View

13.

Lee V, Goedert M, Trojanowski J . Neurodegenerative tauopathies. Annu Rev Neurosci. 2001; 24:1121-59. DOI: 10.1146/annurev.neuro.24.1.1121. View

14.

Liu L, Drouet V, Wu J, Witter M, Small S, Clelland C . Trans-synaptic spread of tau pathology in vivo. PLoS One. 2012; 7(2):e31302. PMC: 3270029. DOI: 10.1371/journal.pone.0031302. View

15.

Meyer V, Dinkel P, Luo Y, Yu X, Wei G, Zheng J . Single mutations in tau modulate the populations of fibril conformers through seed selection. Angew Chem Int Ed Engl. 2014; 53(6):1590-3. PMC: 4083751. DOI: 10.1002/anie.201308473. View

16.

Clavaguera F, Akatsu H, Fraser G, Crowther R, Frank S, Hench J . Brain homogenates from human tauopathies induce tau inclusions in mouse brain. Proc Natl Acad Sci U S A. 2013; 110(23):9535-40. PMC: 3677441. DOI: 10.1073/pnas.1301175110. View

17.

Clavaguera F, Bolmont T, Crowther R, Abramowski D, Frank S, Probst A . Transmission and spreading of tauopathy in transgenic mouse brain. Nat Cell Biol. 2009; 11(7):909-13. PMC: 2726961. DOI: 10.1038/ncb1901. View

18.

BISHOP M, Ferrone F . Kinetics of nucleation-controlled polymerization. A perturbation treatment for use with a secondary pathway. Biophys J. 1984; 46(5):631-44. PMC: 1435060. DOI: 10.1016/S0006-3495(84)84062-X. View

19.

Margittai M, Langen R . Template-assisted filament growth by parallel stacking of tau. Proc Natl Acad Sci U S A. 2004; 101(28):10278-83. PMC: 478563. DOI: 10.1073/pnas.0401911101. View

20.

Furukawa Y, Kaneko K, Nukina N . Tau protein assembles into isoform- and disulfide-dependent polymorphic fibrils with distinct structural properties. J Biol Chem. 2011; 286(31):27236-46. PMC: 3149317. DOI: 10.1074/jbc.M111.248963. View