Quantitative evidence for neurofilament heavy subunit aggregation in motor neurons of spinal cords of patients with amyotrophic lateral sclerosis

amyotrophic lateral sclerosis (als), a neurodegenerative disease of unknown etiology, affects motor neurons leading to atrophy of skeletal muscles, paralysis and death. there is evidence for the accumulation of neurofilaments (nf) in motor neurons of the spinal cord in als cases. nf are major structural elements of the neuronal cytoskeleton. they play an important role in cell architecture and differentiation and in the determination and maintenance of fiber caliber. they are composed of three different polypeptides: light (nf-l), medium (nf-m) and heavy (nf-h) subunits. in the present study, we performed a morphological and quantitative immunohistochemical analysis to evaluate the accumulation of nf and the presence of each subunit in control and als cases. spinal cords from patients without neurological disease and from als patients were obtained at autopsy. in all als cases there was a marked loss of motor neurons, besides atrophic neurons and preserved neurons with cytoplasmic inclusions, and extensive gliosis. in control cases, the immunoreaction in the cytoplasm of neurons was weak for phosphorylated nf-h, strong for nf-m and weak for nf-l. in als cases, anterior horn neurons showed intense immunoreactivity in focal regions of neuronal perikarya for all subunits, although the difference in the integrated optical density was statistically significant only for nf-h. furthermore, we also observed dilated axons (spheroids), which were immunopositive for nf-h but negative for nf-m and nf-l. in conclusion, we present qualitative and quantitative evidence of nf-h subunit accumulation in neuronal perikarya and spheroids, which suggests a possible role of this subunit in the pathogenesis of als.