Synaptic vesicle proteins, synaptophysin and chromogranin A in amyotrophic lateral sclerosis

In amyotrophic lateral sclerosis (ALS) it is not known which motoneuron is affected first. The study of synaptic proteins may contribute to the clarification of the problem. Fifteen cases of ALS and five control cases were studied with the immunohistochemical demonstration of synaptophysin (Sy) and chromogranin A (CgA). Sy is a typical membrane protein of small synaptic vesicles (SSV), whereas CgA is found in large dense core vesicles (LDCV) and in neurosecretory granules. In controls, Sy is distributed as dots on the neuronal surface, on proximal dendrites and in neuropil, whereas CgA is found in perikarya and dendrites and as puncta in the neuropil. In ALS there is a marked decrease of Sy-positive dots. In chromatolytic neurons and spheroids a diffuse reaction may occur. CgA-positive dots disappear in ALS, sometimes replaced by a dust-like positivity. CgA is produced by Golgi apparatus and its reduction in ALS corresponds to the fragmentation of the Golgi complex, described in the literature. The findings are interpreted as secondary to the lower motoneuron degeneration and discussed in relation to our knowledge on vesicle production and migration in the neuron and on synapses in the anterior horns of spinal cord.