Structure of alpha-synuclein fibrils derived from human Lewy body dementia tissue

Dhruva D. Dhavale, Alexander M. Barclay, Collin G. Borcik, Katherine Basore, Deborah A. Berthold, Isabelle R. Gordon, Jialu Liu, Moses H. Milchberg, Jennifer Y. O’Shea, Michael J. Rau, Zachary Smith, Soumyo Sen, Brock Summers, John Smith, Owen A. Warmuth, Richard J. Perrin, Joel S. Perlmutter, Qian Chen, James A.J. Fitzpatrick, Charles D. SchwietersEmad Tajkhorshid, Chad M. Rienstra, Paul T. Kotzbauer

Research output: Contribution to journalArticlepeer-review


The defining feature of Parkinson disease (PD) and Lewy body dementia (LBD) is the accumulation of alpha-synuclein (Asyn) fibrils in Lewy bodies and Lewy neurites. Here we develop and validate a method to amplify Asyn fibrils extracted from LBD postmortem tissue samples and use solid state nuclear magnetic resonance (SSNMR) studies to determine atomic resolution structure. Amplified LBD Asyn fibrils comprise a mixture of single protofilament and two protofilament fibrils with very low twist. The protofilament fold is highly similar to the fold determined by a recent cryo-electron microscopy study for a minority population of twisted single protofilament fibrils extracted from LBD tissue. These results expand the structural characterization of LBD Asyn fibrils and approaches for studying disease mechanisms, imaging agents and therapeutics targeting Asyn.

Original languageEnglish (US)
Article number2750
JournalNature communications
Issue number1
StatePublished - Dec 2024

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


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