Age-dependent formation of TMEM106B amyloid filaments in human brains
Authors
Huang, Melissa
Lövestam, Sofia
Vidal, Ruben
Hallinan, Grace I.
Newell, Kathy L.
Tarutani, Airi
Murayama, Shigeo
Miyazaki, Masayuki
Saito, Yuko
Yoshida, Mari
Hasegawa, Kazuko
Lashley, Tammaryn
Revesz, Tamas
van Swieten, John
Takao, Masaki
Spillantini, Maria Grazia
Murzin, Alexey G.
Publication Date
2022-03-28Journal Title
Nature
ISSN
0028-0836
Publisher
Nature Publishing Group UK
Volume
605
Issue
7909
Pages
310-314
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Schweighauser, M., Arseni, D., Bacioglu, M., Huang, M., Lövestam, S., Shi, Y., Yang, Y., et al. (2022). Age-dependent formation of TMEM106B amyloid filaments in human brains. Nature, 605 (7909), 310-314. https://doi.org/10.1038/s41586-022-04650-z
Abstract
Abstract: Many age-dependent neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, are characterized by abundant inclusions of amyloid filaments. Filamentous inclusions of the proteins tau, amyloid-β, α-synuclein and transactive response DNA-binding protein (TARDBP; also known as TDP-43) are the most common1, 2. Here we used structure determination by cryogenic electron microscopy to show that residues 120–254 of the lysosomal type II transmembrane protein 106B (TMEM106B) also form amyloid filaments in human brains. We determined the structures of TMEM106B filaments from a number of brain regions of 22 individuals with abundant amyloid deposits, including those resulting from sporadic and inherited tauopathies, amyloid-β amyloidoses, synucleinopathies and TDP-43 proteinopathies, as well as from the frontal cortex of 3 individuals with normal neurology and no or only a few amyloid deposits. We observed three TMEM106B folds, with no clear relationships between folds and diseases. TMEM106B filaments correlated with the presence of a 29-kDa sarkosyl-insoluble fragment and globular cytoplasmic inclusions, as detected by an antibody specific to the carboxy-terminal region of TMEM106B. The identification of TMEM106B filaments in the brains of older, but not younger, individuals with normal neurology indicates that they form in an age-dependent manner.
Keywords
Article, /631/535/1258/1259, /631/378/340, /101/28, /13/51, article
Identifiers
s41586-022-04650-z, 4650
External DOI: https://doi.org/10.1038/s41586-022-04650-z
This record's URL: https://www.repository.cam.ac.uk/handle/1810/337089
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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