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Models of environmentally induced neurological disease: epidemiology and etiology of amyotrophic lateral sclerosis and parkinsonism-dementia in the Western Pacific.

Abstract：

:Amyotrophic lateral sclerosis (ALS) on Guam previously attained incidence rates 50 to 100 times that of the continental United States and Europe and accounted for one in five deaths among Chamorros over age 25. A second neurological disorder in high incidence, parkinsonism-dementia (PD), and the early appearance in those populations of neurofibrillary tangles such as are seen in Alzheimer's disease and normal ageing have also been noted. Incidence and mortality rates of both diseases have declined dramatically during the past 30 years, and today, the risk of developing either disease among Guamanian Chamorros is only several times higher than in non-Guamanian populations. The decline is most likely a consequence of increased acculturation over the past three decades, with a concomitant decrease in isolation, changes in dietary habits and local water supplies, and much less dependence on locally grown foodstuffs. Similar declines are evident in the remaining two Pacific foci of high- incidence ALS, namely the Kii Peninsula focus in Japan and southern West New Guinea where western contact and introduction of new foodstuffs have occurred.The accumulating epidemiological, genetic and environmental evidence, as well as the development of new and promising experimental animal models, support the hypothesis that a basic metabolic defect, provoked by chronic nutritional deficiencies of calcium, lead to increased intestinal absorption of toxic metals and the co-deposition of calcium, aluminium and silicon in neurons of patients with ALS and PD. This elemental deposition is thought to result in aberrant microtubule assembly and/or abnormal post-translational modification of the amyloid precursor protein leading to widespread formation of neurofibrillary tangles, the hallmark pathological features in these disorders. The naturalistic paradigms of these foci in the Western Pacific have provided insights to understanding not only ALS and PD but other neurological disorders, such as classical ALS, Parkinson's disease, Alzheimer's disease and early neuronal ageing.

journal_name

Environ Geochem Health

journal_title

Environmental geochemistry and health

authors

Garruto RM,Yanagihara R,Gajdusek DC

doi

10.1007/BF01734063

subject

Has Abstract

pub_date

1990-03-01 00:00:00

pages

137-51

issue

1-2

eissn

0269-4042

issn

1573-2983

journal_volume

pub_type

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Models of environmentally induced neurological disease: epidemiology and etiology of amyotrophic lateral sclerosis and parkinsonism-dementia in the Western Pacific.