Familial amyotrophic lateral sclerosis and parkinsonism-dementia complex of the Kii peninsula of Japan: Clinical and neuropathological study and tau analysis

We report the first case of neuropathologically verified parkinsonism-demen tia complex of the Kii peninsula, together with the patient's brother, who had amyotrophic lateral sclerosis. The propositus woman developed parkinson ism and dementia at 63 years of age and died at 70 without displaying clini cal features of amyotrophic lateral sclerosis. The brain exhibited marked a trophy of the frontal and temporal lobes. Microscopically, there were many neurofibrillary tangles in the central nervous system, most markedly in the mesial temporal lobe and deep nuclei, as well as changes of amyotrophic la teral sclerosis but no senile plaques or Lewy bodies. Neurofibrillary tangl es exhibited twisted tubule structures on electon microscopic examination, and an analysis of insoluble tau protein extracted from the fresh brain rev ealed a 60-, 64-, 68-kD triplet. The tau gene exhibited no mutations. Her b rother developed progressive bulbar palsy-type amyotrophic lateral sclerosi s at 45 years of age and died at 49 without presenting with dementia or par kinsonism. Neuropathological examination revealed not only pathologic featu res of amyotrophic lateral sclerosis but also a moderate number of neurofib rillary tangles in the temporal cortex and deep nuclei. The siblings were n europathologically similar despite their different clinical manifestations. These findings suggest that amyotrophic lateral sclerosis and parkinsonism -dementia complex of this family may be phenotypic variants of a tauopathy caused by genetic abnormalities.