Amyotrophic lateral sclerosis/parkinsonism-dementia complex of the Kii peninsula of Japan (Kii ALS/PDC) may be a familial tauopathy. Epidemiological trends, clinical features, neuropathology and molecular genetics

Abstract

The Kii peninsula of Japan and the island of Guam in the western Pacific are two major foci of very high prevalence rates of amyotrophic lateral sclerosis (ALS) in the world [1, 2]. ALS accumulated in some villages on Guam and in the Kii peninsula at rates 50-100 times of those in the other areas of the United States or Japan. Another peculiar endemic disease parkinsonism-dementia complex (PDC), also accumulates at very high prevalence rates in the same areas. PDC is characterized by progressive parkinsonism and dementia clinically and by loss of nerve cells and marked neurofibrillary degeneration without accompanying senile plaques neuropathologically [3]. Many neurofibrillary tangles (NFTs) are seen in the temporal lobe cortex, substantia nigra, and brainstem nuclei, and a few in the cerebellum and spinal cord in ALS and PDC on Guam [4] and ALS in the Kii peninsula foci [5]. ALS and PDC in the western Pacific have thus been regarded as being two different clinical phenotypes of a nosologically single disease.