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. 2022 May 5;143(6):613–640. doi: 10.1007/s00401-022-02426-3

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© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — Ultrastructural and biochemical characterization of pathogenic TDP-43 extracted from human TDP-43 proteinopathies. Immunohistochemistry of brain section from patients with TDP-43 proteinopathies, stained with pS409/pS410 antibody. a Neuronal cytoplasmic inclusions (NCIs) and short degenerative neurites (DNs) in FTLD-TDP Type A. b NCIs in FTLD-TDP Type B. c Long DNs in FTLD-TDP Type C. Scale bar, 50 μm. d Immunoelectron microscopy of sarkosyl-insoluble fractions extracted from FTLD-TDP (type A, type B, type C) patients. Electron micrographs show fibrous structures with 10–15 nm in diameter positive for pS409/pS410, after labeling with secondary antibody conjugated to 5 nm gold particles. Scale bar, 50 nm. e Immunoblot analyses of sarkosyl-insoluble fractions prepared from brains of patients withTDP-43 proteinopathies. Sarkosyl-insoluble phosphorylated TDP-43 (45 kDa) was detected with pS409/410 antibody. Subtype-specific C-terminal fragments were also observed: 18, 19, 23, 24 and 26 kDa bands in type A, 18, 19, 23, 24 and 26 kDa bands in type B, 18, 19, 23 and 24 kDa bands in type C. All data are original for this review