Modifications of microtubule proteins in ALS nerve precede detectable histologic and ultrastructural changes

Fast axonal transport is altered in nerves from amyotrophic lateral sclerosis (ALS) patients. Microtubules are involved in axonal transport. We analyzed the possibility of an involvement of microtubule modifications underlying the alterations in transport using biochemical and morphologic analysis of intercostal nerves from ALS and control patients. In intercostal nerves displaying no morphologic signs of acute neuronal degeneration, two-dimensional gels showed modifications of the group of beta tubulins and abnormal spots of proteins, some appearing to be closely related to tau proteins. These results suggest that microtubule proteins are modified in ALS before ultrastructural axonal degeneration, but the significance of these abnormalities remains hypothetical.