Clinicopathological studies of some non-Alzheimer dementing diseases

The brains of most demented patients show at autopsy the lesions of Alzheimer's disease (AD). However, the brains of other demented patients show either no morphological changes or lesions distinct from those of AD. We report clinicopathological studies on two diseases in this latter group. The study of these diseases can improve our understanding of AD. Pick's disease is characterized by dementia, lobar cerebral atrophy, and neuronal cytoplasmic inclusions. Most cases, which we have called "classical", show inclusions made up of straight fibrils that are immunologically cross-reactive with the paired helical filaments of AD. In other "generalized" cases, similar fibrils are coated by granular material and are less reactive with anticytoskeletal antibodies. In contrast to the cytoplasmic localization of the lesions in Pick's disease, it is the cell nucleus that shows abnormalities in neuronal intranuclear hyaline inclusion disease. This disease can present clinically as dementia of adult onset. Thus, either nuclear or cytoplasmic lesions can produce a pattern of neuronal dysfunction resulting in dementia.