Guamanian neurodegenerative disease

Ahlskog, J. Eric; Waring, Stephen; Lt, Kurland; Petersen, Ronald C.; Moyer, Thomas P.; Harmsen, William S.; Maraganore, Demetrius M.; O’Brien, Peter C.; Esteban-Santillan, C.; Bush, Vannevar

doi:10.1212/wnl.45.7.1340

Cited by 49 publications

(21 citation statements)

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“…Low levels of calcium in water, it was suggested, triggered a parathyroid response that promoted gut absorption of calcium, with the result that absorption of “neurotoxic bystanders”, such as aluminum, would also take place [19]. While aluminum and other metals can be detected in the brain of Guam ALS-PDC patients, parathyroid function is unremarkable [20]. Additionally, in West Papua, ALS prevalence in a sessile, riverine population has declined without any known change in their source of drinking water [9].…”

Section: Evidence For the Role Of Cycads In Als-pdcmentioning

confidence: 99%

Is Neurodegenerative Disease a Long-Latency Response to Early-Life Genotoxin Exposure?

Kisby

Spencer

2011

IJERPH

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Western Pacific amyotrophic lateral sclerosis and parkinsonism-dementia complex, a disappearing neurodegenerative disease linked to use of the neurotoxic cycad plant for food and/or medicine, is intensively studied because the neuropathology (tauopathy) is similar to that of Alzheimer’s disease. Cycads contain neurotoxic and genotoxic principles, notably cycasin and methylazoxymethanol, the latter sharing chemical relations with nitrosamines, which are derived from nitrates and nitrites in preserved meats and fertilizers, and also used in the rubber and leather industries. This review includes new data that influence understanding of the neurobiological actions of cycad and related genotoxins and the putative mechanisms by which they might trigger neurodegenerative disease.

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Section: Evidence For the Role Of Cycads In Als-pdcmentioning

confidence: 99%

Is Neurodegenerative Disease a Long-Latency Response to Early-Life Genotoxin Exposure?

Kisby

Spencer

2011

IJERPH

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“…Deficient nutritional intake of calcium, associated with absorption and neuronal deposition of aluminum and other metals, has been advanced as causal [1,6,12] but, on Guam, calcium concentrations in river water and indigenous food plants are unremarkable [13]. Aluminum seems to accumulate variably in affected nerve cells and conceivably may play a role in the disease [14]; however, experimental animals chronically treated with aluminum fail to develop clinical or neuropathological signs of the western Pacific disease [1].…”

Section: Cycad Hypothesismentioning

confidence: 99%

Damage and Repair of Nerve Cell Dna in Toxic Stress*

Kisby

Kabel

Hugon

et al. 1999

Drug Metabolism Reviews

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“…There has been no positive evidence for HLA, blood type, enzymes in red blood cells, serum proteins, immunoglobulin polymorphism [5], polymorphism of apolipoprotein E gene [18] or genetic abnormalities of Cu/Zn SOD [3] and Tau protein [22].As for environmental factors, extensive studies based on calcium, heavy metal or cycad hypotheses [1,25,26] failed to disclose the evidences supporting any of these substances as a major causative factor in the development of ALS/PDC.…”

Section: Discussionmentioning

confidence: 99%

A clinical and pathological study of a Japanese case of Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex with family history

Konagaya

Kato

Sakai

et al. 2003

Journal of Neurology

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This report concerns a Japanese family with neuropathological findings consistent with amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) in the Island of Guam. The proband was a 68-year-old woman with an 8-year history of parkinsonism which was followed by psychiatric symptoms and neurogenic amyotrophy 5 years after the onset. She had a family history of parkinsonism associated with dementia in all of her three siblings. They grew up in the Hobara village, a focus of amyotrophic lateral sclerosis in the Kii Peninsula of Japan in their childhood. Their parents were not consanguineous nor natives of the Kii Peninsula. The brain weight was 1040 g and there were mild frontal lobe atrophy, moderate atrophy of pes hippocampi, decoloration of the substantia nigra and locus coeruleus, and atrophy of the anterior root of the spinal cord. The microscopic examinations revealed degeneration of CA1 portion of the hippocampus to the parahippocampus gyrus, substantia nigra, locus coeruleus and spinal anterior horn with Bunina bodies. The spinal pyramidal tracts also mildly degenerated. Neurofibrillary tangles (NFT) were observed in the cerebral cortex, especially in the cortices from hippocampus to lateral occipitotemporal gyri, basal nucleus of Mynert, basal ganglia, thalamus, substantia nigra and widespread regions of the central nervous system through the brainstem to spinal cord including the nucleus of Onufrowitcz. In spite of a small amount of the senile plaques in the cerebral cortex and Lewy bodies in the substantia nigra and locus coeruleus, abundant NFT were distributed mainly in the third layer of the cerebral cortex, which is the characteristic feature of ALS/PDC. Thus, this was likely to be an ALS/PDC case outside the Guam Island. A tau mutation was not found on DNA analysis.

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Guamanian neurodegenerative disease

Abstract: We could find no evidence in support of abnormalities of calcium metabolism or heavy metal absorption as a major causative factor in the development of neurodegenerative disease on the island of Guam.

Cited by 49 publications

References 0 publications

Is Neurodegenerative Disease a Long-Latency Response to Early-Life Genotoxin Exposure?

Is Neurodegenerative Disease a Long-Latency Response to Early-Life Genotoxin Exposure?

Damage and Repair of Nerve Cell Dna in Toxic Stress*

A clinical and pathological study of a Japanese case of Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex with family history

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