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Characterization of tau pathologies in gray and white matter of Guam parkinsonism-dementia complex

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Abstract

Guam parkinsonism-dementia complex (PDC) is a neurodegenerative tauopathy in ethnic Chamorro residents of the Mariana Islands that manifests clinically with parkinsonism as well as dementia and is characterized neuropathologically by prominent cortical neuron loss in association with extensive telencephalic neurofibrillary tau pathology. To further characterize cortical gray and white matter tau, alpha-synuclein and lipid peroxidation pathologies in Guam PDC, we examined the brains of 17 Chamorro PDC and control subjects using biochemical and immunohistological techniques. We observed insoluble tau pathology in both gray and white matter of PDC and Guam control cases, with frontal and temporal lobes being most severely affected. Using phosphorylation dependent anti-tau antibodies, abundant tau inclusions were detected by immunohistochemistry in both neuronal and glial cells of the neocortex, while less alpha-synuclein pathology was observed in more limited brain regions. Further, in sharp contrast to Alzheimer’s disease (AD), levels of the lipid peroxidation product 8, 12–iso-iPF2α-VI isoprostane were not elevated in Guam PDC brains relative to controls. Thus, although the tau pathologies of Guam PDC share similarities with AD, the composite Guam PDC neuropathology profile of tau, alpha-synuclein and 8, 12-iso-iPF2α-VI isoprostane reported here more closely resembles that seen in other tauopathies including frontotemporal dementias (FTDs), which may imply that Guam PDC and FTD tauopathies share underlying mechanisms of neurodegeneration.

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Acknowledgements

The authors acknowledge support for their research from the NIH (AG14382) and thank the Chamorro families of the patients studied here for making this research possible. JQT is the William Maul Measy-Truman G. Schnabel Jr. M.D. Professor of Geriatric Medicine and Gerontology. VM-YL is the John H. Ware 3rd Chair of Alzheimer’s Disease Research at the University of Pennsylvania.

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Authors and Affiliations

  1. The Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Maloney 3rd Floor, Philadelphia, PA, 19104-4283, USA

    Matthew J. Winton, Sonali Joyce, Victoria Zhukareva, John Q. Trojanowski & Virginia M. -Y. Lee

  2. Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Domenico Practico, John Q. Trojanowski & Virginia M. -Y. Lee

  3. Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Domenico Practico

  4. Departments of Pathology and Psychiatry, Mt. Sinai School of Medicine, New York, NY, USA

    Daniel P. Perl

  5. Department of Neuroscience, University of California at San Diego, San Diego, CA, USA

    Douglas Galasko

  6. Department of Neuroscience, University of Guam, Guam, Mariana Islands

    Ula Craig

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  1. Matthew J. Winton
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Correspondence to Virginia M. -Y. Lee.

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Winton, M.J., Joyce, S., Zhukareva, V. et al. Characterization of tau pathologies in gray and white matter of Guam parkinsonism-dementia complex. Acta Neuropathol 111, 401–412 (2006). https://doi.org/10.1007/s00401-006-0053-0

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  • DOI: https://doi.org/10.1007/s00401-006-0053-0

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