HUNTINGTIN LOCALIZATION IN BRAINS OF NORMAL AND HUNTINGTONS-DISEASE PATIENTS

The immunohistochemical localization of huntingtin was examined in the Huntington's disease (HD) brain with an antibody that recognizes the wild-type and mutant proteins. Neuronal staining was reduced in areas of the HD striatum depleted of medium-sized neurons; large striatal ne urons, which are spared in HD, retained normal levels of huntingtin ex pression. Neuronal labeling was markedly reduced in both segments of t he globus pallidus including in brains with minimal loss of pallidal n eurons. In some HD cortical and striatal neurons with normal looking m orphology, huntingtin was associated with punctate cytoplasmic granule s that at the ultrastructural level resembled the multivesicular body, an organelle involved in retrograde transport and protein degradation . Some immunoreactive processes showed blebbing and segmentation simil ar to that induced experimentally by hypoxic-ischemic or excitotoxic i njury. Huntingtin staining was more concentrated in the perinuclear cy toplasm and reduced or absent in processes of atrophic cortical neuron s. Nuclear staining was also evident. Fibers in the subcortical white matter of HD patients had significantly increased huntingtin immunorea ctivity compared with those of controls. Results suggest that there ma y be changes in the neuronal expression and transport of wild-type and /or mutant huntingtin at early and late stages of neuronal degeneratio n in affected areas of the HD brain.