Neurodegenerative Disorders among the Chamorro People of Guam: Studies of an Isolate in Transition

Abstract

During the past three decades we have recognized a unique opportunity to study high-incidence foci of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD) in non-western anthropological populations in the Pacific Basin aimed at identifying their etiology and mechanism of pathogenesis and their relationship to other neurodegenerative disorders, such as Alzheimer’s disease, parkinsonism, and early neuronal aging. Pacific ALS and PD are two progressive and fatal neurological disorders that occur hyperendemically in different cultures, in different ecological zones and among genetically divergent populations in the Mariana Islands, in the Kii Peninsula of Japan and in southern West New Guinea. Our cross-disciplinary approach to these intriguing neurological disorders and the accumulated epidemiological, cellular and molecular evidence strongly implicate environmental factors in their causation, specifically the role of aluminum and its interaction with calcium. The remaining question is whether the clinical expressions of these disorders are solely environmentally induced or whether they represent a genetic susceptibility combined with an “environmental trigger”. The dramatic decline of these disorders in all three high-incidence foci over the past 40 years can be supported by both models. A clearer understanding of these natural paradigms will surely have far-reaching implications for Alzheimer’s disease and other disorders with long latency and slow progression. In this paper we concentrate our efforts on the Guamanian focus of ALS and PD which is far and away the best studied of the three high incidence Pacific foci and summarize the results of familial and genetic studies conducted during the past 30 years on Guam.