Skip Navigation


Brain Advance Access originally published online on April 17, 2007
Brain 2007 130(5):1386-1394; doi:10.1093/brain/awm065
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
130/5/1386    most recent
awm065v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (45)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Hasegawa, M.
Right arrow Articles by Oyanagi, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hasegawa, M.
Right arrow Articles by Oyanagi, K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author (2007). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

TDP-43 is deposited in the Guam parkinsonism–dementia complex brains

Masato Hasegawa1,*, Tetsuaki Arai2,*, Haruhiko Akiyama2, Takashi Nonaka1, Hiroshi Mori3, Tomoyo Hashimoto4, Mineo Yamazaki4 and Kiyomitsu Oyanagi4

1Departments of Molecular Neurobiology and 2Psychogeriatrics, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, 3Department of Neuroscience, Osaka City University School of Medicine, 1-4-3 Asahimachi, Abenoku, Osaka 545-8585 and 4Department of Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo Metropolitan Organization for Medical Research, 2-6 Musashidai, Fuchu, Tokyo 183-8526, Japan

Correspondence to: Masato Hasegawa and Tetsuaki Arai, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan E-mail: masato{at}prit.go.jp

TDP-43, a nuclear factor that functions in regulating transcription and alternative splicing, was recently identified as a component of the ubiquitin-positive, tau-negative inclusions specific for frontotemporal lobar degeneration (FTLD-U) and amyotrophic lateral sclerosis (ALS). In the present study, we carried out immunohistochemical and biochemical analyses of brains of Guamanians with the parkinsonism–dementia complex (G-PDC) using anti-TDP-43, anti-tau and anti-ubiquitin antibodies. Immunohistochemistry with anti-TDP-43 antibodies revealed various types of positive structures in the frontotemporal and hippocampal regions of G-PDC cases. Most of these structures were negative for tau. By immunoblot analysis with the TDP-43 antibody, an abnormal 45 kDa band, as well as a diffuse staining throughout the gel, was detected in the sarkosyl-insoluble fractions of G-PDC brains. Dephosphorylation has shown that abnormal phosphorylation takes place in the accumulated TDP-43 seen in FTLD-U and ALS. These results suggest that accumulation of TDP-43 is a common process in certain neurodegenerative disorders, including FTLD-U, ALS and G-PDC.

Key Words: frontotemporal lobar degeneration; amyotrophic lateral sclerosis; ubiquitin; tau; inclusion

Abbreviations: ALS, amyotrophic lateral sclerosis; FTLD-U, frontotemporal lobar degeneration; G-PDC, Guam parkinsonism–dementia complex; NCI, neuronal cytoplasmic inclusions; NII, neuronal intranuclear inclusions

.

Received January 29, 2007. Revised March 7, 2007. Accepted March 8, 2007.

*These authors contributed equally to this work.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Arch NeurolHome page
C.-E. Yu, T. D. Bird, L. M. Bekris, T. J. Montine, J. B. Leverenz, E. Steinbart, N. M. Galloway, H. Feldman, R. Woltjer, C. A. Miller, et al.
The Spectrum of Mutations in Progranulin: A Collaborative Study Screening 545 Cases of Neurodegeneration
Arch Neurol, February 1, 2010; 67(2): 161 - 170.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
L. M. Igaz, L. K. Kwong, Y. Xu, A. C. Truax, K. Uryu, M. Neumann, C. M. Clark, L. B. Elman, B. L. Miller, M. Grossman, et al.
Enrichment of C-Terminal Fragments in TAR DNA-Binding Protein-43 Cytoplasmic Inclusions in Brain but not in Spinal Cord of Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis
Am. J. Pathol., July 1, 2008; 173(1): 182 - 194.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
K. A. Josephs, J. L. Whitwell, D. S. Knopman, W. T. Hu, D. A. Stroh, M. Baker, R. Rademakers, B. F. Boeve, J. E. Parisi, G. E. Smith, et al.
Abnormal TDP-43 immunoreactivity in AD modifies clinicopathologic and radiologic phenotype
Neurology, May 6, 2008; 70(19_Part_2): 1850 - 1857.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
J. Sreedharan, I. P. Blair, V. B. Tripathi, X. Hu, C. Vance, B. Rogelj, S. Ackerley, J. C. Durnall, K. L. Williams, E. Buratti, et al.
TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis
Science, March 21, 2008; 319(5870): 1668 - 1672.
[Abstract] [Full Text] [PDF]

Home page
 Arch NeurolHome page
M. Neumann, L. K. Kwong, D. M. Sampathu, J. Q. Trojanowski, and V. M.-Y. Lee
TDP-43 Proteinopathy in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis: Protein Misfolding Diseases Without Amyloidosis
Arch Neurol, October 1, 2007; 64(10): 1388 - 1394.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.