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Nat Med. 2014 Aug;20(8):881-5. doi: 10.1038/nm.3617. Epub 2014 Jul 20.

Huntington's disease is a four-repeat tauopathy with tau nuclear rods.

Author information

1
1] Center for Molecular Biology "Severo Ochoa" (CBMSO) Consejo Superior de Investigaciones Científicas y Universidad Autónoma de Madrid (CSIC/UAM), Madrid, Spain. [2] Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Spain.
2
1] Center for Molecular Biology "Severo Ochoa" (CBMSO) Consejo Superior de Investigaciones Científicas y Universidad Autónoma de Madrid (CSIC/UAM), Madrid, Spain. [2] Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Spain. [3].
3
Department of Pathology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
4
1] Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Spain. [2] Institute of Neuropathology, Bellvitge Biomedical Research Institute (IDIBELL)-University Hospital Bellvitge, University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain.

Abstract

An imbalance of tau isoforms containing either three or four microtubule-binding repeats causes frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) in families with intronic mutations in the MAPT gene. Here we report equivalent imbalances at the mRNA and protein levels and increased total tau levels in the brains of subjects with Huntington's disease (HD) together with rod-like tau deposits along neuronal nuclei. These tau nuclear rods show an ordered filamentous ultrastructure and can be found filling the neuronal nuclear indentations previously reported in HD brains. Finally, alterations in serine/arginine-rich splicing factor-6 coincide with tau missplicing, and a role of tau in HD pathogenesis is evidenced by the attenuation of motor abnormalities of mutant HTT transgenic mice in tau knockout backgrounds.

PMID:
25038828
DOI:
10.1038/nm.3617
[Indexed for MEDLINE]

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