Axonal transport of dopamine-β-hydroxylase and acetylcholinesterase in human peripheral neuropathy

The content and axonal transport of dopamine-β-hydroxylase (DBH) were measured in biopsy samples of sural nerve from 20 normal subjects and from more than 50 patients with various types of peripheral neuropathy. In a smaller series of cases the dynamics of acetylcholinesterase (AChE) were also examined. Judged from the rate of accumulation of enzyme activity against a ligature during incubation in vitro, the normal average transport velocity of DBH was 1.8 mm/h. However, only 25% of the enzyme appeared to be transported and true velocity was estimated at 7.2 mm/h. Similar calculations placed the normal average velocity of AChE at 1.0 mm/h, the amount transported at 14%, and the true velocity at 7.1 mm/h. Statistically significant reductions in average transport velocity of DBH were observed in nerves from patients with hereditary sensory neuropathy types I and II and with hereditary motor and sensory neuropathy types II and III. In the latter condition (Déjerine - Sottas disease) transport was almost zero although the DBH activity per unit weight of nerve was normal. Significant reduction in average transport velocity of DBH but normal enzyme content was also observed in uremic neuropathy. In nerves from patients with diabetic neuropathy, both content and average velocity of DBH were reduced, and likewise those of AChE. Because the size of the transported fractions of these enzymes appeared normal in the diabetic nerves, the reduced average velocity probably reflected a real slowing of transport. These observations make it likely that rapid axonal transport of proteins is compromised in certain types of peripheral nerve disease in man.