INVOLVEMENT OF THE AMYGDALA, DENTATE AND HIPPOCAMPUS IN MOTOR-NEURON DISEASE

A pathological hallmark of motor neuron disease (MND) is the presence of ubiquitinated inclusions in lower motor neurons. Recently, ubiquiti n-immunoreactive inclusions have been found in neocortical and hippoca mpal neurons, indicating that in some cases there may be extensive ext ra-motor involvement. We have observed that some cases of MND with dem entia (MND-D), had ubiquitinated inclusions in the amygdala. In order to study this systematically, we examined 18 cases of 'typical' MND, 4 cases of MND-D and 12 neurologically normal and abnormal controls, us ing antibodies against ubiquitin and a range of cytoskeletal proteins. In addition to standard neuropathological examination, we examined in detail the anterior thalamus, parahippocampal gyrus, dentate gyrus of the hippocampus, and the amygdala. We found ubiquitin immunoreactive inclusions in the amygdala and parahippocampal gyrus in more than 30% of MND cases, most of whom were not known to have significant cognitiv e impairment. These inclusions did not react with antibodies against t au or with phosphorylated neurofilaments. They thus differ from the in clusions of Alzheimer's disease, and they do not have the appearance o r immunocytochemical features of cortical Lewy bodies. In parallel stu dies we have found selective cognitive impairments in about 25% of our patients with typical MND, and PET activation studies show impaired a ctivation in the anterior thalamus, parahippocampal gyrus and medial f rontal regions. Since the amygdala is an important source of afferents for the limbic system, its involvement may be one of the factors unde rlying both cognitive changes and PET abnormalities.