Amyloid fibrils in FTLD-TDP are composed of TMEM106B and not TDP-43

Yi Xiao Jiang, Qin Cao, Michael R. Sawaya, Romany Abskharon, Peng Ge, Michael DeTure, Dennis W. Dickson, Janine Y. Fu, Rachel R. Ogorzalek Loo, Joseph A. Loo and David S. Eisenberg ()
Additional contact information
Yi Xiao Jiang: UCLA-DOE Institute, and Molecular Biology Institute, UCLA
Qin Cao: UCLA-DOE Institute, and Molecular Biology Institute, UCLA
Michael R. Sawaya: UCLA-DOE Institute, and Molecular Biology Institute, UCLA
Romany Abskharon: UCLA-DOE Institute, and Molecular Biology Institute, UCLA
Peng Ge: UCLA-DOE Institute, and Molecular Biology Institute, UCLA
Michael DeTure: Mayo Clinic
Dennis W. Dickson: Mayo Clinic
Janine Y. Fu: UCLA-DOE Institute, and Molecular Biology Institute, UCLA
Rachel R. Ogorzalek Loo: UCLA-DOE Institute, and Molecular Biology Institute, UCLA
Joseph A. Loo: UCLA-DOE Institute, and Molecular Biology Institute, UCLA
David S. Eisenberg: UCLA-DOE Institute, and Molecular Biology Institute, UCLA

Nature, 2022, vol. 605, issue 7909, 304-309

Abstract: Abstract Frontotemporal lobar degeneration (FTLD) is the third most common neurodegenerative condition after Alzheimer’s and Parkinson’s diseases1. FTLD typically presents in 45 to 64 year olds with behavioural changes or progressive decline of language skills2. The subtype FTLD-TDP is characterized by certain clinical symptoms and pathological neuronal inclusions with TAR DNA-binding protein (TDP-43) immunoreactivity3. Here we extracted amyloid fibrils from brains of four patients representing four of the five FTLD-TDP subclasses, and determined their structures by cryo-electron microscopy. Unexpectedly, all amyloid fibrils examined were composed of a 135-residue carboxy-terminal fragment of transmembrane protein 106B (TMEM106B), a lysosomal membrane protein previously implicated as a genetic risk factor for FTLD-TDP4. In addition to TMEM106B fibrils, we detected abundant non-fibrillar aggregated TDP-43 by immunogold labelling. Our observations confirm that FTLD-TDP is associated with amyloid fibrils, and that the fibrils are formed by TMEM106B rather than TDP-43.

Date: 2022
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41586-022-04670-9 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:605:y:2022:i:7909:d:10.1038_s41586-022-04670-9

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-022-04670-9

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().