FAMILIAL PARKINSONISM AND DEMENTIA WITH BALLOONED NEURONS, ARGYROPHILIC NEURONAL INCLUSIONS, ATYPICAL NEUROFIBRILLARY TANGLES, TAU-NEGATIVEASTROCYTIC FIBRILLARY TANGLES, AND LEWY BODIES

We report four patients with a new type of familial parkinsonism and d ementia consisting of an autosomal dominant inheritance, dopa-responsi ve parkinsonism, severe dementia, variable myoclonus and autonomic dis turbances. Autopsy of two patients revealed symmetrical cerebral atrop hy with fronto-temporal dominant distribution, and marked depigmentati on in the substantia nigra and locus ceruleus. Neuronal loss and glios is were observed in the deep cerebral cortex and amygdala as well as i n the areas vulnerable to Parkinson's disease. In the cerebral cortex, swollen neurons with frequent granulovacuolar changes were observed, consisting of ballooned neurons and those with argyrophilic intracytop lasmic inclusions, in addition to neuropil threads. Atypical neurofibr illary tangles, which barely stained with tau antibodies, were numerou s in the upper cortical layers, consisting of 15-nm straight tubules. In addition, tau-negative astrocytic fibrillary tangles were also freq uent. Electron microscopically, the ballooned neurons and argyrophilic neuronal inclusions contained filamentous structures coated with fuzz y electron-dense deposits, The inclusions showed immunohistochemical f eatures different from those of cortical Lewy bodies and Pick bodies. Occasional Lewy bodies were present in the brain stem lesions of both patients. In two of our patients, the pathology in the brain stem was similar to that of Parkinson's disease, whereas their cerebral patholo gy was unusual and has not been reported previously.