FRAGMENTATION OF THE GOLGI-APPARATUS OF MOTOR-NEURONS IN AMYOTROPHIC-LATERAL-SCLEROSIS (ALS) - CLINICAL-STUDIES IN ALS OF GUAM AND EXPERIMENTAL STUDIES IN DEAFFERENTED NEURONS AND IN BETA,BETA'-IMINODIPROPIONITRILE AXONOPATHY

Previous morphological immunpenzymatic studies with organelle-specific antibodies have disclosed an apparent fragmentation of the Golgi appa ratus in large numbers of motor neurons in 12 cases of sporadic, non-G uamanian amyotrophic lateral sclerosis (ALS) in three cases of other t ypes of motor neuron disease and in one case of a mitochondrial myopat hy with cytochrome c oxidase deficiency. Motor neurons with fragmented Golgi apparatus were moderately atrophic; in these cells, discrete im munostained elements of the organelle were twice as many as in normal neurons, and the size of each Golgi element and the percentage of the cytoplasmic area occupied by the Golgi apparatus were reduced (Am J Pa thol 1992, 140: 731-737). In this report we have confirmed the fragmen tation of the organelle of motor neurons in the spinal cord in six spo radic cases of Guamanian ALS. In four of the six cases the clinical co urse was 1 to 2 years. The percentages of motor neurons with fragmente d Golgi apparatus varied from 38 to 92. Motor neurons from three addit ional cases of Guamanian ALS of clinical duration from 5 to 7 years di d not show fragmentation of the Golgi apparatus In two cases of Guaman iannnln ALS and in one non-Gunmanian ALS, all neurons with ubiquitin-p ositive skein-like or granular inclusions believed to be pathognomonic for ALS had fragmented Golgi apparatus. To examine whether the fragme ntation of the Golgi apparatus results from reactions to either neuron al deafferentation or to lesions of proximal axons, we conducted two e xperimental studies. In the first study, we examined in cats the Golgi apparatus of deafferented neurons of the dorsal lateral geniculate nu cleus. In the second study, we examined the Golgi apparatus of motor n eurons in the spinal cord of rats with proximal axonopathy induced by beta,beta'-iminodipropionitrile. In these two experiments, the neurona l Golgi apparatus studied by immunoenzymatic techniques and morphometr y, was not fragmented. Taken together, the results of these studies st rongly suggest that the fragmentation of the Golgi apparatus of motor neurons ons in ALS represents an important tnnt and perhaps early chan ge of the organelle that may be involved in the pathogenesis of ALS. T he fragmentation of the Golgi apparatus of Motor neurons is a fairly s pecific and easily recognizable marker of ALS and may be used together with other criteria for comparisons between the human disease and pro posed animal models of the disorder.