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)
- 523 Downloads
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.
KeywordsAlzheimer’s disease α-Synuclein β-Amyloid protein Coiled body Neurofibrillary tangles Parkinsonism Tau TDP-43
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.
Electronic supplementary material (MPG 264 kb)
- 1.Buée L, Pérez-Tur J, Leveugle B, Buée-Scherrer V, Mufson EJ, Loerzel AJ, Chartier-Harlin MC, Perl DP, Delacourte A, Hof PR (1996) Apolipoprotein E in Guamanian amyotrophic lateral sclerosis/parkinsonism–dementia complex: genotype analysis and relationships to neuropathological changes. Acta Neuropathol 91:247–253PubMedCrossRefGoogle Scholar
- 11.Guiroy DC, Mellini M, Miyazaki M, Hilbich C, Safar J, Garruto RM, Yanagihara R, Beyreuther K, Gajdusek DC (1993) Neurofibrillary tangles of the Guamanian amyotrophic lateral sclerosis, parkinsonism–dementia and neurologically normal Guamanians contain a 4-to 4.5 kilodalton protein which is immunoreactive to anti-amyloid beta/A4-protein antibodies. Acta Neuropathol 86(3):265–274PubMedCrossRefGoogle Scholar
- 15.Hirano A, Kurland LT, Krooth RS, Lessel S (1961) Parkinsonism–dementia complex, an endemic disease on the island of Guam. I. Clin Features Brain 84:642–661Google Scholar
- 18.Hirano A, Dembitzer HM, Kurland LT, Zimmerman HM (1968) The fine structure of some intraganglionic alterations: neurofibrillary tangles, granulovacuolar bodies, and “rod-like” structures as seen in Guam amyotrophic lateral sclerosis and parkinsonism–dementia complex. J Neuropathol Exp Neurol 27:167–182PubMedCrossRefGoogle Scholar
- 20.Hof PR, Nimchinsky EA, Buée-Scherrer V, Buée L, Nasrallah J, Hottinger AF, Purohit DP, Loerzel AJ, Steele JC, Delacourte A et al (1994) Amyotrophic lateral sclerosis/parkinsonism–dementia complex of Guam: quantitative neuropathology, immunohistochemical analysis of neuronal vulnerability, and comparison with related neurodegenerative disorders. Acta Neuropathol 88:397–404PubMedCrossRefGoogle Scholar
- 29.Mulder DW, Kurland LT, Iriarte LLG (1954) Neurological diseases on the island of Guam. US Armed Forces Med J 5:1724–1739Google Scholar
- 32.Oyanagi K, Makifuchi T, Ohtoh T, Chen KM, Gajdusek DC, Chase TN, Ikuta F (1994) The neostriatum and nucleus accumbens in parkinsonism–dementia complex of Guam: a pathological comparison with Alzheimer’s disease and progressive supranuclear palsy. Acta Neuropathol 88:122–128PubMedCrossRefGoogle Scholar
- 34.Pérez-Tur J, Buée L, Morris HR, Waring SC, Onstead L, Wavrant-De Vrièze F, Crook R, Buée-Scherrer V, Hof PR, Petersen RC, McGeer PL, Delacourte A, Hutton M, Siddique T, Ahlskog JE, Hardy J, Steele JC (1999) Neurodegenerative diseases of Guam: analysis of TAU. Neurology 53:411–413PubMedGoogle Scholar
- 37.Schmidt ML, Lee VM, Saido T, Perl D, Schuck T, Iwatsubo T, Trojanowski JQ (1998) Amyloid plaques in Guam amyotrophic lateral sclerosis/parkinsonism–dementia complex contain species of A beta similar to those found in the amyloid plaques of Alzheimer’s disease and pathological aging. Acta Neuropathol 95:117–122PubMedCrossRefGoogle Scholar
- 46.Zimmerman H (1945) Progress report of work in the laboratory of pathology during May 1945. Guam. US Naval Medical Research Unit Number 2, 1 June. Washington, DCGoogle Scholar