Alzheimer's disease (AD) is characterized neuropathologically by high densities of neurofibrillary tangles (NFT) and neuritic plaques (NP) in the cerebral cortex, in particular in neocortical association areas and in the hippocampal formation. We report here the case of an AD patient who developed signs of motor dysfunction early in the clinical evolution. A quantitative neuropathologic analysis revealed much higher densities of NFT and NP in the primary motor cortex than is usually observed in AD. This case, together with other reports, points to the existence of neurologically defined subgroups of AD with unusual clinical deficits that are correlated with the regional and laminar distribution of NP and NFT, and further supports the hypothesis that the symptomatology presented by AD patients results from the loss of specific neuronal populations leading to a syndrome of global cortical disconnection. (J Geriatr Psychiatry Neurol 1992;5:85–92).