Synaptic pathology of spinal anterior horn cells in amyotrophic lateral sclerosis: an immunohistochemical study.

We have applied immunohistochemical techniques to study synaptic alterations of the spinal anterior horn in amyotrophic lateral sclerosis (ALS), and other disorders involving upper or lower motor neurons. A monoclonal antibody to synaptophysin was used. Spinal cord tissues from normal individuals served as controls. As compared to these, a decrease in synaptophysin immunoreactivity was evident in the neuropil in the spinal anterior horn of ALS patients. However, synaptophysin expression in the perikarya and dendrites of remaining normal-appearing neurons in these patients was not decreased and occasionally it was even higher than in control neurons. Similar results were obtained with specimens from patients with lower motor neuron disease. Synaptophysin immunoreactivity in the neuropil and perikarya of the cases with focal spinal cord lesions with bilateral descending tract degeneration was similar to normal controls. Our data suggest that the alterations in synaptophysin expression occurring in ALS are mainly associated with the loss of lower motor neurons, and that the occasional increased perikaryal expression may be due to the neuronal atrophy, compensatory accumulation or abnormal synaptic vesicle degradation.