Original Article

Unexpected abundance of pathological tau in progressive supranuclear palsy white matter

  1. Victoria Zhukareva PhD1,
  2. Sonali Joyce BS1,
  3. Teresa Schuck BS1,
  4. Vivianna Van Deerlin MD, PhD1,
  5. Howard Hurtig MD2,
  6. Roger Albin MD3,4,
  7. Sid Gilman MD, FRCP3,
  8. Steven Chin MD5,
  9. Bruce Miller MD6,
  10. John Q. Trojanowski MD, PhD1,
  11. Virginia M-Y. Lee PhD1,*

Article first published online: 5 JUL 2006

DOI: 10.1002/ana.20916

Issue

Annals of Neurology

Annals of Neurology

Volume 60, Issue 3, pages 335–345, September 2006

Additional Information

How to Cite

Zhukareva, V., Joyce, S., Schuck, T., Van Deerlin, V., Hurtig, H., Albin, R., Gilman, S., Chin, S., Miller, B., Trojanowski, J. Q. and Lee, V. M.-Y. (2006), Unexpected abundance of pathological tau in progressive supranuclear palsy white matter. Ann Neurol., 60: 335–345. doi: 10.1002/ana.20916

Author Information

  1. 1

    Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Philadelphia, PA

  2. 2

    Department of Neurology, University of Pennsylvania, Philadelphia, PA

  3. 3

    Michigan Alzheimer's Disease Research Center, University of Michigan Health Center, Ann Arbor, MI

  4. 4

    Ann Arbor Affairs Medical Center Geriatric Research Education and Clinical Center, Ann Arbor, MI

  5. 5

    Department of Pathology, University of Utah, Salt Lake City, UT

  6. 6

    Memory and Aging Center of the University of California, San Francisco, CA

*The Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, HUP/Maloney 3, 3600 Spruce Street, Philadelphia, PA 19104-4283

Publication History

  1. Issue published online: 18 SEP 2006
  2. Article first published online: 5 JUL 2006
  3. Manuscript Accepted: 9 MAY 2006
  4. Manuscript Revised: 25 APR 2006
  5. Manuscript Received: 5 JAN 2006

Funded by

  • National Institute of Aging. Grant Numbers: AG-10124, AG08671, AG-17586
  • Oxford Foundation
  • Marian S. Ware Alzheimer Program of the University of Pennsylvania

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Abstract

Objective

To investigate whether biochemical insoluble tau with 4 (4R) and/or 3 (3R) microtubule-binding repeats accumulate in white as well as gray matter in progressive supranuclear palsy (PSP), a neurodegenerative tauopathy.

Methods

To assess tau pathology in PSP white matter, we combined Western blot (WB) and immunohistochemical methods to analyze 23 autopsy-confirmed PSP brains.

Results

WBs showed an unexpected abundance of insoluble tau in white and gray matter of PSP brains, but biochemical tau pathology in white matter was not correlated with immunohistochemistry using the same panel of epitope-specific anti-tau antibodies used for WB. Despite heterogeneity in the representation of pathological 3R and 4R tau isoforms in cortical versus subcortical regions, biochemically detectable white matter tau pathology is a constant feature of PSP.

Interpretation

These studies show additional similarities between PSP and corticobasal degeneration, but unlike corticobasal degeneration, more abundant white matter tau pathology in PSP is detectable by WB than by immunohistochemistry. The differential detection of abnormal tau by biochemistry versus microscopy in PSP may reflect distinct pathological mechanisms, and elucidation of these processes will augment efforts to develop better strategies for the diagnosis and treatment of PSP and related neurodegenerative tauopathies. Ann Neurol 2006

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