Early loss of neostriatal striosome neurons in Huntington's disease

• Published in: Journal of neuropathology and experimental neurology Vol. 54; no. 1; p. 105
• Main Authors: Hedreen, J C, Folstein, S E
• Format: Journal Article
• Language: English
• Published: England 01-01-1995
• Subjects: Astrocytes - pathology; Cadaver; Cell Death; Corpus Striatum - metabolism; Corpus Striatum - pathology; Glial Fibrillary Acidic Protein - metabolism; Humans; Huntington Disease - metabolism; Huntington Disease - pathology; Immunohistochemistry; Neurons - pathology; Time Factors
• ISSN: 0022-3069
• DOI: 10.1097/00005072-199501000-00013

During the first years of symptomatic Huntington's disease (HD), no readily apparent pathology is seen in the neostriatum at autopsy. To investigate the pathological correlates of chorea and other early clinical signs, we examined the evolution of neuronal loss and accompanying astrocytosis in neostriatal tissue from autopsy cases of early HD. We found scattered islands of astrocytosis and neuronal loss that were present before the previously described ventrally progressive wave of generalized neuronal loss. Histological demonstration of these islands, which are apparently specific to HD, is very helpful in the pathological differential diagnosis of this disease. Immunocytochemical stains for glial fibrillary acidic protein and for markers of the neostriatal striosome-matrix system showed that these islands correspond to the striosome compartment. Striosomal neuronal loss was present throughout the dorsoventral extent of the caudate nucleus and putamen during the early phase of symptomatic disease, and this loss extended to the most ventral region of the nucleus accumbens in later stages. Analysis of the functional circuitry of the basal ganglia suggests that early degeneration of striosomal neurons may produce hyperactivity of the nigrostriatal dopaminergic pathway, causing chorea and other early clinical manifestations of HD.