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Acta Neuropathologica

, 116:625 | Cite as

Enduring involvement of tau, β-amyloid, α-synuclein, ubiquitin and TDP-43 pathology in the amyotrophic lateral sclerosis/parkinsonism–dementia complex of Guam (ALS/PDC)

  • Judith Miklossy
  • John C. Steele
  • Sheng Yu
  • Sherman McCall
  • Glenn Sandberg
  • Edith G. McGeer
  • Patrick L. McGeerEmail author
Original Paper

Abstract

Guam ALS/PDC is a severe tangle forming disorder endemic to Guam with features overlapping such neurodegenerative disorders as Alzheimer disease (AD), Parkinson disease (PD), progressive supranuclear palsy (PSP), ALS, corticobasal degeneration (CBD) and pallido-ponto-nigral degeneration (PPND). Since the prevalence is declining, we examined brain tissue from 35 clinically diagnosed Chamorro patients with ALS/PDC and two Chamorro controls autopsied between 1946 and 2006, to determine if distinct variations in the pathology could be identified up to this time. Although the age at autopsy increased by 4.5–5 years per decade, we identified no qualitative differences in pathological deposits with antibodies against tau, ubiquitin, Aβ, α-synuclein and TDP-43, indicating that these more recently identified proteins have been involved in the neuropathogenesis over the past 6 decades. Tau and TDP-43 positive neuronal, oligodendroglial and astrocytic inclusions involving multiple nerve fiber tracts occurred in both the ALS and PDC types, reinforcing the concept that these forms are part of the same disorder. The results obtained may help to define the commonality of the Guam disease with other tangle forming disorders and may help in monitoring the epidemiological changes that are taking place.

Keywords

Alzheimer’s disease α-Synuclein β-Amyloid protein Coiled body Neurofibrillary tangles Parkinsonism Tau TDP-43 

Notes

Acknowledgments

This paper was supported by a Grant from the Pacific Alzheimer Research Foundation. We thank H. Akiyama, L. Binder, B. Giasson, H. Mori and K. Obi for their generous gifts of key antibodies and H. Martin and J. P. Guo for technical assistance in preparing figures.

Supplementary material

Electronic supplementary material (MPG 264 kb)

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Judith Miklossy
    • 1
  • John C. Steele
    • 2
  • Sheng Yu
    • 1
  • Sherman McCall
    • 3
  • Glenn Sandberg
    • 4
  • Edith G. McGeer
    • 1
  • Patrick L. McGeer
    • 1
    Email author
  1. 1.Kinsmen Laboratory of Neurological ResearchThe University of British ColumbiaVancouverCanada
  2. 2.Guam Memorial HospitalTamuningUSA
  3. 3.United States Army Medical Research Institute for Infectious Diseases (USAMRIID)FrederickUSA
  4. 4.Armed Forces Institute of PathologyWashington, DCUSA

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