Distribution of inclusions in neuronal nuclei and dystrophic neurites in huntington disease brain

Recently, an N-terminal fragment of huntingtin was localized to neuronal in tranuclear inclusions (NII), presumed to cause cellular dysfunction, and to inclusions in dystrophic neurites (IDN) in the neostriatum and neocortex o f Huntington disease (HD) patients. In the present immunohistochemical stud y of autopsy brain of 2 juvenile-onset HD patients, 5 HD patients with adul t-onset, and 5 controls, NII and IDN as stained with both N-terminal antise rum to huntingtin and ubiquitin antiserum were detected in the HD neostriat um, neocortex, and allocortex, but not in the HD pallidum, cerebellum, and substantia nigra nor in control brain. The frequency of NII in the HD neoco rtex was highest in the juvenile patients. Within the allocortex, NII and I DN were found in the entorhinal region, subiculum, and pyramidal cell layer of Ammon's horn. N-terminal huntingtin antiserum also labeled intranuclear granular structures adjacent to the neuronal nuclear membrane in 5 HD pati ents, one control with idiopathic epilepsy, and one with Alzheimer disease. Our results show that NII formation in HD involves the allocortex in addit ion to the neostriatum and neocortex. The development of NII in the neocort ex and allocortex in HD brain might contribute to the emergence of the cogn itive and behavioral symptoms of the disease.