Familial nature and continuing morbidity of the amyotrophic lateral sclerosis-parkinsonism dementia complex of Guam

Chamorros suffer from two neurologic syndromes known as ALS and the parkinsonism-dementia complex (PDC) of Guam. We report mortality figures for these syndromes during 1991 to 1995 and compare them with those at 5-year intervals dating back to 1951. In contrast to predictions of disease disappearance, both syndromes remain prevalent. However, age of onset and age at death have increased for both syndromes, suggesting that shifting environmental factors are causing disease postponement. We also report the clinical, familial, neuropathologic, and immunohistochemical findings on a consecutive autopsy series of Guamanian Chamorro cases. Twelve cases were diagnosed as PDC, known locally as ''bodig,'' and three as ALS, known locally as ''lytico.'' All but three of these fifteen patients had a pronounced family history of similar illness. Eight of twelve bodig patients had siblings who were also affected with bodig; two of three lytico cases had siblings afflicted with lytico. The family histories are compatible with genetic transmission of each syndrome. The neuropathology of bodig is characterized by severe and widespread neurofibrillary tangle (NFT) development. NFTs are surrounded by reactive microglia and reactive astrocytes, and complement proteins and other molecules connected with inflammation are associated with them. Similar inflammatory responses also occur in Alzheimer's disease (AD) but have been largely attributed to the presence of senile plaques. These data indicate that tangles, as well as plaques, generate inflammatory reactions and that such reactions may exacerbate the fundamental pathology in bodig as well as in AD.