Skip to main content
SpringerLink
Log in

Amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam: quantitative neuropathology, immunohistochemical analysis of neuronal vulnerability, and comparison with related neurodegenerative disorders

  • Regular Paper
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

Amyotrophic lateral sclerosis/parkinsonism-dementia complex (lytico-bodig) is a chronic neurodegenerative disorder with high prevalence among the native Chamorro population of Guam. Neuropathological, biochemical, and immunohistochemical analyses were performed on a relatively large series of Guamanian cases and compared to Alzheimer's disease cases. Thioflavin S and antibodies to amyloid βA4 and tau proteins were used for analysis of pathological changes, and antibodies to the calcium-binding proteins parvalbumin and calretinin, and to a nonphosphorylated epitope on neurofilament protein to study select neuronal populations. A differential distribution of neurofibrillary tangles was observed in the neocortex of Guamanian cases compared to Alzheimer's disease cases, with much higher lesion counts in supragranular than in infragranular layers. Also, Guamanian cases with predominant parkinsonism had generally higher neurofibrillary tangle densities than cases with predominant amyotrophic lateral sclerosis. In addition, there was a certain degree of heterogeneity, qualitatively and quantitatively, in the biochemical distribution of tau proteins among Guamanian and Alzheimer's disease cases as revealed by Western blot analysis. Previous studies have suggested that the clinical symptomatology observed in patients suffering from Alzheimer's disease is related to the dramatic loss of specific corticocortically projecting neurons in the neocortex. Interestingly, a subset of neurofilament-rich pyramidal neurons known to be dramatically affected in Alzheimer's disease appears to be resistant in lytico-bodig. Finally, as in Alzheimer's disease, calcium-binding protein-containing interneurons are not affected. These data suggest that the set of projection neurons affected in Guamanian cases may not correspond to those involved in Alzheimer's disease, and that both disorders are characterized by specific patterns of neuronal vulnerability.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Arai H, Noguchi I, Makino Y, Kosaka K, Heizmann CW, Iizuka R (1991) Parvalbumin-immunoreactive neurons in the cortex in Pick's disease. J Neurol 238:200–202

    PubMed  Google Scholar 

  2. Barbas H (1986) Patterns in the laminar origin of corticocortical connections. J Comp Neurol 252:415–422

    PubMed  Google Scholar 

  3. Behrouz N, Défossez A, Delacourte A, Hublau P, Mazzuca M (1989) Alzheimer's disease: glycolytic pretreatment dramatically enhances immunolabeling of senile plaques and cerebrovascular amyloid substance. Lab Invest 61:576–583

    PubMed  Google Scholar 

  4. Buée-Scherrer V, Buée L, Vermersch P, Hof PR, Leveugle B, Loerzel A, Steele JC, Delacourte A, Perl DP (1993) Biochemical characterization of the tau proteins in amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) of Guam. Soc Neurosci Abstr 19:195

    Google Scholar 

  5. Chen KM, Chase TN (1986) Parkinsonism-dementia. Handb Clin Neurol 49:167–183

    Google Scholar 

  6. Choi DW (1988) Glutamate neurotoxicity and diseases of the nervous system. Neuron 1:623–634

    Article  PubMed  Google Scholar 

  7. Cudkowicz M, Kowall NW (1990) Parvalbumin-immunoreactive neurons are resistant to degeneration in Huntington's disease cerebral cortex. J Neuropathol Exp Neurol 49: 345

    Google Scholar 

  8. Défossez A, Beauvillain JC, Delacourte A, Mazzuca M (1988) Alzheimer's disease: a new evidence for common epitopes between microtubule-associated protein tau and paired helical filaments (PHF): demonstration at the electron microscope by a double immunogold labeling. Virchows Arch [A] 413:141–145

    Google Scholar 

  9. Delacourte A, Flament S, Dibe EM, Hublau P, Sablonnière B, Hémon B, Scherrer V, Défossez A (1990) Pathological protein Tau 64 and 69 are specifically expressed in the somatodendritic domain of the degenerating cortical neurons during Alzheimer's disease: demonstration with a panel of antibodies against tau proteins. Acta Neuropathol 80:111–117

    Article  PubMed  Google Scholar 

  10. Elizan TS, Hirano A, Abrams BM, Need RL, Van Nuis C, Kurland LT (1966) Amyotrophic lateral sclerosis and parkinsonism-dementia complex of Guam — Neurological reevaluation. Arch Neurol 14:356–368

    PubMed  Google Scholar 

  11. Felleman DJ, Van Essen DC (1991) Distributed hierarchical processing in the primate cerebral cortex. Cereb Cortex 1: 1–47

    PubMed  Google Scholar 

  12. Ferrer I, Soriano E, Tuñón T, Fonseca M, Guionnet N (1991) Parvalbumin immunoreactive neurons in normal human temporal neocortex and in patients with Alzheimer's disease. J Neurol Sci 106:135–141

    Article  PubMed  Google Scholar 

  13. Flament S, Delacourte A, Verny M, Hauw JJ, Javoy-Agid F (1991) Abnormal tau proteins in progressive supranuclear palsy — Similarities and differences with the neurofibrillary degeneration of the Alzheimer type. Acta Neuropathol 81: 591–596

    Article  PubMed  Google Scholar 

  14. Garruto RM, Yase Y (1986) Neurodegenerative disorders of the Western Pacific: the search for mechanisms of pathogenesis. Trends Neurosci 9:368–371

    Article  Google Scholar 

  15. Gentleman SM, Perl DP, Allsop D, Clinton J, Royston MC, Roberts GW (1991) β(A4)-amyloid protein and parkinsonian-dementia complex of Guam. Lancet 337:55–56

    Article  Google Scholar 

  16. Good PF, Perl DP, Bierer LM, Schmeidler J (1992) Selective accumulation of aluminum and iron in the neurofibrillary tangles of Alzheimer's disease: a laser microprobe (LAMMA) study. Ann Neurol 31:286–292

    PubMed  Google Scholar 

  17. Hauw JJ, Verny M, Delaère P, Cervera P, He Y, Duyckaerts C (1990) Constant neurofibrillary changes in the neocortex of progressive supranuclear palsy. Basic differences with Alzheimer's disease and aging. Neurosci Lett 119:182–186

    Article  PubMed  Google Scholar 

  18. Hirano A, Llena J (1986) Neuropathological features of parkinsonism-dementia complex on Guam: reappraisal and comparative study with Alzheimer's disease and Parkinson's disease. Prog Neuropathol 6:17–31

    Google Scholar 

  19. Hirano A, Kurland LT, Krooth RS, Lessell S (1961) Parkinsonism-dementia complex, an endemic disease on the island of Guam. I. Clinical features. Brain 84:642–661

    PubMed  Google Scholar 

  20. Hirano A, Malamud N, Elizan TS, Kurland LT (1966) Amyotrophic lateral sclerosis and parkinsonism-dementia complex on Guam-Further pathologic studies. Arch Neurol 15:35–51

    PubMed  Google Scholar 

  21. Hirano A, Malamud N, Kurland LT (1966) Parkinsonism-dementia complex, an endemic disease on the island of Guam. II. Pathological features. Brain 84:662–679

    Google Scholar 

  22. Hof PR, Morrison JH (1991) Neocortical neuronal subpopulations labeled by a monoclonal antibody to calbindin exhibit differential vulnerability in Alzheimer's disease. Exp Neurol 111:293–301

    Article  PubMed  Google Scholar 

  23. Hof PR, Cox K, Morrison JH (1990) Quantitative analysis of a vulnerable subset of pyramidal neurons in Alzheimer's disease I. Superior frontal and inferior temporal cortex. J Comp Neurol 301:44–54

    PubMed  Google Scholar 

  24. Hof PR, Cox K, Young WG, Celio MR, Rogers J, Morrison JH (1991) Parvalbumin-immunoreactive neurons in the neocortex are resistant to degeneration in Alzheimer's disease. J Neuropathol Exp Neurol 50:451–462

    PubMed  Google Scholar 

  25. Hof PR, Perl DP, Loerzel AJ, Morrison JH (1991) Neurofibillary tangle distribution in the cerebral cortex of parkinsonism-dementia cases from Guam: differences with Alzheimer's disease. Brain Res 564:306–313

    Article  PubMed  Google Scholar 

  26. Hof PR, Delacourte A, Bouras C (1992) Distribution of cortical neurofibrillary tangles in progressive supranuclear palsy: a quantitative analysis of six cases. Acta Neuropathol 84: 45–51

    PubMed  Google Scholar 

  27. Hof PR, Charpiot A, Delacourte A, Buée L, Purohit D, Perl DP, Bouras C (1992) Distribution of neurofibrillary tangles in the cerebral cortex in postencephalitic parkinsonism. Neurosci Lett 139:10–14

    Article  PubMed  Google Scholar 

  28. Hof PR, Nimchinsky EA, Celio MR, Bouras C, Morrison JH (1993) Calretinin-immunoreactive neocortical interneurons are unaffected in Alzheimer's disease. Neurosci Lett 152: 145–149

    Article  PubMed  Google Scholar 

  29. Ince P, Stout N, Shaw P, Slade J, Hunziker W, Heizmann CW, Baimbridge KG (1993) Parvalbumin and calbindin D-28k in the human motor system and in motor neuron disease. Neuropathol Appl Neurobiol 19:291–299

    PubMed  Google Scholar 

  30. Kurland LT (1988) Amyotrophic lateral sclerosis and Parkinson's disease complex on Guam linked to an environmental toxin. Trends Neurosci 11:51–54

    Article  PubMed  Google Scholar 

  31. Lee VMY, Balin BJ, Otvos L Jr, Trojanoswki JQ (1991) A68: a major subunit of paired helical filaments and derivatized form of normal tau. Science 251:675–678

    PubMed  Google Scholar 

  32. Lepore FE, Steele JC, Cox TA, Tillson G, Calne DB, Duvoisin RC, Lavine L, McDarby JV (1988) Supranuclear disturbances of ocular motility in Lytico-Bodig. Neurology 38: 1849–1853

    PubMed  Google Scholar 

  33. Lewis DA, Campbell MJ, Terry RD, Morrison JH (1987) Laminar and regional distribution of neurofibrillary tangles and neuritic plaques in Alzheimer's disease: a quantitative study of visual and auditory cortices. J Neurosci 7:1799–1808

    PubMed  Google Scholar 

  34. Morrison JH, Lewis DA, Campbell MJ, Huntley GW, Benson DL, Bouras C (1987) A monoclonal antibody to nonphosphorylated neurofilament protein marks the vulnerable cortical neurons in Alzheimer's disease. Brain Res 416: 331–336

    Article  PubMed  Google Scholar 

  35. Morrison JH, Vickers JC, Huntley GW, Brose N, Gasic GP, Jahn R, Heinemann SF (1993) Differential distribution of NMDAR1 immunoreactivity in prefrontal and entorhinal cortices of monkey and human. Soc Neurosci Abstr 19:472

    Google Scholar 

  36. Nihei K, McKee AC, Kowall NW (1993) Patterns of neuronal degeneration in the motor cortex of amyotrophic lateral sclerosis patients. Acta Neuropathol 86:55–64

    PubMed  Google Scholar 

  37. Pearson RCA, Esiri MM, Hiorns RW, Wilcock GK, Powell TPS (1985) Anatomical correlates of the distribution of the pathological changes in the neocortex in Alzheimer's disease. Proc Natl Acad Sci USA 82:4531–4534

    PubMed  Google Scholar 

  38. Perl DP (1985) Relationship of aluminum to Alzheimer's disease. Environ Health Perspect 63:149–153

    PubMed  Google Scholar 

  39. Perl DP, Brody AR (1980) Alzheimer's disease: X-ray spectrometric evidence of aluminum accumulation in neurofibrillary tangle-bearing neurons. Science 208:297–299

    PubMed  Google Scholar 

  40. Perl DP, Gajdusek DC, Garruto RM, Yanagihara RT, Gibbs CJ (1982) Intraneuronal aluminum accumulation in amyotrophic lateral sclerosis and parkinsonism-dementia of Guam. Science 217:1053–1055

    PubMed  Google Scholar 

  41. Rogers J, Morrison JH (1985) Quantitative morphology and regional and laminar distributions of senile plaques in Alzheimer's disease. J Neurosci 5:2801–2808

    PubMed  Google Scholar 

  42. Spencer PS, Nunn PB, Hugon J, Ludolph AC, Ross SM, Roy DN, Robertson RC (1987) Guam amyotrophic lateral sclerosis-parkinsonism-dementia linked to a plant excitant neurotoxin. Science 237:517–522

    PubMed  Google Scholar 

  43. Terry RD, Peck A, DeTeresa R, Schechter R, Horoupian DS (1981) Some morphometric aspects of the brain in the senile dementia of the Alzheimer type. Ann Neurol 10:184–192

    PubMed  Google Scholar 

  44. Vermersch P, Robitaille Y, Berniez L, Wattez A, Gauvreau D, Delacourte A (1994) Biochemical mapping of neurofibrillary degeneration in a case of progressive supranuclear palsy: evidence for general cortical involvement. Acta Neuropathol 87: 572–577

    Article  PubMed  Google Scholar 

  45. Vickers JC, Delacourte A, Morrison JH (1992) Progressive transformation of the cytoskeleton associated with normal aging and Alzheimer's disease. Brain Res 594:273–278

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurobiology, Mount Sinai School of Medicine, 10029, New York, NY, USA

    P. R. Hof, E. A. Nimchinsky, A. F. Hottinger, C. Bouras, J. H. Morrison & D. P. Perl

  2. Department of Geriatrics and Adult Development, Mount Sinai School of Medicine, 10029, New York, NY, USA

    P. R. Hof, A. Delacourte & J. H. Morrison

  3. INSERM Unité 156, Place de Verdun, F-59045, Lille, France

    V. Buée-Scherrer, L. Buée & A. Delacourte

  4. Department of Pathology, Mount Sinai School of Medicine, 10029, New York, NY, USA

    J. Nasrallah, A. F. Hottinger, D. P. Purohit & D. P. Perl

  5. Guam Memorial Hospital, 96910, Agaña, Guam, USA

    A. J. Loerzel & J. C. Steele

  6. Micronesian Health Survey, 96923, Mangilao, Guam, USA

    J. C. Steele

  7. Department of Psychiatry, IUPG Belle-Idée, University of Geneva School of Medicine, CH-1225, Geneva, Switzerland

    C. Bouras

  8. Department of Psychiatry, Mount Sinai School of Medicine, 10029, New York, NY, USA

    D. P. Perl

Authors
  1. P. R. Hof
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. A. Nimchinsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. Buée-Scherrer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. Buée
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Nasrallah
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. F. Hottinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. D. P. Purohit
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A. J. Loerzel
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J. C. Steele
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. A. Delacourte
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. C. Bouras
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. J. H. Morrison
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. D. P. Perl
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported by NIH grants AG08802, AG05138 and AG06647, the Brookdale Foundation, and the France-Alzheimer Association

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hof, P.R., Nimchinsky, E.A., Buée-Scherrer, V. et al. Amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam: quantitative neuropathology, immunohistochemical analysis of neuronal vulnerability, and comparison with related neurodegenerative disorders. Acta Neuropathol 88, 397–404 (1994). https://doi.org/10.1007/BF00389490

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00389490

Key words

Search

Navigation