[Lessons from Guam ALS/PDC study].
An extraordinarily high incidence of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC) affecting the native population was discovered on the island of Guam a half century ago. Guam ALS is identical to classic ALS clinically and pathologically while PDC is marked by progressive parkinsonism and dementia. The unusual histological finding in these fetal neurodegenerative diseases is the presence of numerous neurofibrillary tangles in a selective topographic distribution unassociated with senile plaques. There have been remarkable advances in field of age-associated neurodegenerative disease after our initial study of Guam cases. Four noteworthy topics are presented in this communication. 1) Clinically, the coexistence of parkinsonism and dementia was frequently recognized in Parkinson disease and Alzheimer disease. Some other new disease entities characterized by coexistence of parkinsonism and dementia have been reported. These include progressive supranuclear palsy, frontotemporal dementia and parkinsonism linked to chromosome 17. 2) Neuropathologically, abundant neurofibrillary tangles unassociated with senile plaques were demonstrated in many diseases such as aftermath of boxing and tangle-only dementia. Furthermore, tau-positive structures were recognized not only in neurons but in glial cells in certain diseases. Tauopathy is one of the current hot research subjects. 3) Familial aggregation of Guam ALS patients provoked investigation of familial ALS elsewhere. Familial motor neuron disease with SOD1 mutation is the target of worldwide intense investigation at the present time. SOD1 gene mutation is, however, not found in Guam ALS. 4) The most striking findings of the Guam study is the gradual decline in the incidence of ALS on Guam during a quarter century and virtual disappearance of new patients. This may be linked to a remarkable change in environment and life style of the Chamorro population. The etiology of ALS is still unknown and no new treatment is available. Guam ALS/PDC is certainly one of the most mysterious riddles among age-associated neurodegenerative diseases during the last half a century.
Asao
Hirano
H
Division of Neuropathology, Montefiore Medical Center, Bronx, New York 10467-2490, USA.
D000690:Amyotrophic Lateral Sclerosis / Q000150:complications* / Q000453:epidemiology; D003704:Dementia / Q000150:complications* / Q000453:epidemiology; D006141:Guam / Q000453:epidemiology; D006801:Humans; D020734:Parkinsonian Disorders / Q000150:complications* / Q000453:epidemiology; D012106:Research