Amyotrophic lateral sclerosis and parkinsonism‐dementia on Guam

Rodgers-Johnson, P.; Garruto, Ralph M.; Yanagihara, R; Chen, K.-M.; Gajdusek, D. C.; Gibbs, Clarence J.

doi:10.1212/wnl.36.1.7

Cited by 123 publications

(40 citation statements)

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“…ALS on Guam, clinically similar to classical ALS, was confirmed to be a dinstinct and endemic entity among the indigenous Chamorro population of Guam in the 1950s [2, [3][4][5]. The onset of symptoms is insidious with atrophy, weakness, and fasciculations of striated musculature [6,7]. Muscle weakness and atrophy are progressive and result in flaccid paralysis, often within a year of onset of the disease.…”

Section: Clinical Featuresmentioning

confidence: 99%

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Neuroepidemiologic Research Initiatives on Guam: Past and Present

Wiederholt

1999

Neuroepidemiology

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Since the middle of this century, a remarkable concentration of cases of neurodegenerative disease(s), referred to as amyotrophic lateral sclerosis and Parkinson-dementia complex (ALS/PDC), has been recognized among Chamorro natives of Guam. Intense investigations over the last 4 decades have failed to determine the etiology of these invariably fatal diseases. Over the same time period, the incidence of ALS has decreased dramatically, the incidence of PDC has decreased, but to a lesser degree, and age at onset has shifted to a later age by about 1 decade. Almost 50% of demented patients present without the classical Parkinsonian features of PDC, and the morphological picture has changed. Results of past and present research initiatives are reviewed.

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Section: Clinical Featuresmentioning

confidence: 99%

“…Muscle weakness and atrophy are progressive and result in flaccid paralysis, often within a year of onset of the disease. In contrast to classical ALS, the Guam form of ALS occurred at a younger age, and both extrapyramidal features and dementia were present in up to 10% of patients [6,8,9].…”

Section: Clinical Featuresmentioning

confidence: 99%

Neuroepidemiologic Research Initiatives on Guam: Past and Present

Wiederholt

1999

Neuroepidemiology

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“…For example, cognitive dysfunction and extrapyramidal symptoms are observed in patients with corticobasal degeneration or progressive supranuclear palsy. In the Guam amyotrophic lateral sclerosis-parkinsonism-dementia complex, 2 and in a subset of frontotemporal dementia, 3 patients present with motorneuron disease and dementia. Although most cases of familial frontotemporal dementia have been recently found to be caused by mutations in the progranulin gene, pathogenic mutations in the tau gene have also been identified in familial forms of frontotemporal lobar degeneration.…”

mentioning

confidence: 99%

Early Axonopathy Preceding Neurofibrillary Tangles in Mutant Tau Transgenic Mice

Leroy

Bretteville

Schindowski

et al. 2007

The American Journal of Pathology

120

105

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Neurodegenerative diseases characterized by brain and spinal cord involvement often show widespread accumulations of tau aggregates. We have generated a transgenic mouse line (Tg30tau) expressing in the forebrain and the spinal cord a human tau protein bearing two pathogenic mutations (P301S and G272V). These mice developed age-dependent brain and hippocampal atrophy, central and peripheral axonopathy, progressive motor impairment with neurogenic muscle atrophy, and neurofibrillary tangles and had decreased survival. Axonal spheroids and axonal atrophy developed early before neurofibrillary tangles. Neurofibrillary inclusions developed in neurons at

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“…The initial procedure was done using the method of Ihara et al (15). The second purification procedure was done according to the method described by Masters et al (12) and modified for NFT isolation (10 (1,16,17). Congo red staining of neurons and isolated NFT revealed typical green birefringence for these four specimens and was negative for the control tissue.…”

Section: Methodsmentioning

confidence: 99%

Amyloid of neurofibrillary tangles of Guamanian parkinsonism-dementia and Alzheimer disease share identical amino acid sequence.

Guiroy¹,

Miyazaki²,

Multhaup³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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The presence of abundant intraneuronal amyloid in the form of neurofibrillary tangles (NFT) in the brains of Guamanian parkinsonism-dementia patients and the absence of extraneuronal amyloid in the form of vascular amyloid deposits or senile plaques permit the purification of NH without contamination with extraneuronal amyloid. Thus, we have isolated and determined the amino acid sequence of the polypeptide subunit of the amyloid fibrils of these NFT and describe their ultrastructure. The NFT, which consist of single and paired helical filaments, similar to those of Alzheinier disease, and occasionally triple helical filaments, are composed of multimeric aggregates of a polypeptide of 42 amino acids (A4 protein). The relative molecular mass of the subunit protein, 4.0-4.5 kDa, is the same as the molecular mass of the amyloid of NFT, of the amyloid plaque cores, and of vascular amyloid deposits in Alzheimer disease and Down syndrome; the sequence of 15 amino acid residues at the N-terminus of the amyloid fibrils in the NFT of Guamanian parkinsonismdementia is identical to that of the amyloid of NFT, amyloid plaque cores, and cerebrovascular deposits in Alzheimer disease and Down syndrome. Furthermore, the heterogeneity, or variation in polypeptide length, of the N-terminus of the amyloid of Guamanian parkinsonism-dementia is the same as in Alzheimer disease and Down syndrome. Our observations indicate that the brain amyloids of these diseases have a common subunit protein, which would also indicate a common pathogenesis.We report here the ultrastructure of purified neurofibrillary tangles (NFT) of Guamanian parkinsonism-dementia (PD), its subunit molecular mass, subunit amino acid composition, and the partial amino acid sequence of the N-terminus. In Guamanian PD extracellular amyloid deposits in the form of senile plaques, and deposits of amyloid in vascular walls are absent, whereas typical NFT are abundant in many brain areas (1-4). The absence of senile plaques and vascular amyloid deposits, which could contaminate the purification procedure for NFT, makes Guamanian PD brain tissue an excellent preparation for the study of NFT free from other forms of brain amyloid.Previous studies indicate a close ultrastructural similarity between the NFT of Alzheimer disease (AD) and that of Guamanian PD (2,3,5,6 (10)(11)(12) have shown that in both AD and Down syndrome (DS) (i) the intraneuronal paired helical filaments (PHF) forming NFT, (ii) the extracellular amyloid fibrils of amyloid plaque cores, and (iii) the vascular amyloid deposits are all composed of an amyloid subunit protein (A4) of 4.0-4.5 kDa that contains similar amino acids and has an identical 42-amino acid sequence. The heterogeneity, or variation in polypeptide length, at the N terminus in the intraneuronal amyloid fibrils of NFT is common to both diseases. This variation is considerably less in the extracellular amyloid fibrils of amyloid plaque cores (10-12), and Glenner and Wong found no N-terminal heterogeneity in vascular amyloid (13,14,22)...

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Amyotrophic lateral sclerosis and parkinsonism‐dementia on Guam

Cited by 123 publications

References 0 publications

Neuroepidemiologic Research Initiatives on Guam: Past and Present

Neuroepidemiologic Research Initiatives on Guam: Past and Present

Early Axonopathy Preceding Neurofibrillary Tangles in Mutant Tau Transgenic Mice

Amyloid of neurofibrillary tangles of Guamanian parkinsonism-dementia and Alzheimer disease share identical amino acid sequence.

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