Huntington disease (HD) is characterized by the loss of striatal projection neurons, which constitute the vast majority of striatal neurons. To determine whether there is differential loss among different populations of striatal projection neurons, the integrity of the axon terminal plexuses arising from the different populations of substance P-containing and enkephalin-containing striatal projection neurons was studied in striatal target areas by immunohistochemistry. Analysis of 17 HD specimens indicated that in early and middle stages of HD, enkephalin-containing neurons projecting to the external segment of the globus pallidus were much more affected than substance P-containing neurons projecting to the internal pallidal segment. Furthermore, substance P-containing neurons projecting to the substantia nigra pars reticulata were more affected than those projecting to the substantia nigra pars compacta. At the most advanced stages of the disease, projections to all striatal target areas were depleted, with the exception of some apparent sparing of the striatal projection to the substantia nigra pars compacta. These findings may explain some of the clinical manifestations and pharmacology of HD. They also may aid in identifying the neural defect underlying HD and provide additional data with which to evaluate current models of HD pathogenesis.Huntington disease (HD) is an autosomal dominant neurodegenerative disorder characterized by choreiform movements, cognitive decline, and personality disturbance (1). The underlying genetic defect in HD is unknown, but the gene has been localized to the short arm of chromosome 4 (2). The histopathology of HD reveals cell loss and astrogliosis in several brain areas, with the most prominent alterations occurring in the striatum (3-5). Although the pathogenetic mechanism of this process is unknown, endogenous "excitotoxins" have been proposed as the mechanism of cell death (6-8). Recent findings indicate that striatal neurons are not uniformly affected in HD and that somatostatin-neuropeptide Y-containing interneurons and cholinergic interneurons are relatively spared (8, 9). Striatal interneurons, however, constitute only a small fraction of the total number of striatal neurons, and it has not been possible to correlate the preservation of interneuron populations with the clinical features of HD.The great majority of striatal neurons are projection neurons, which are heterogeneous in terms of their projection targets and in terms of the neuropeptides they contain (10, 11). These neurons show the earliest evidence of abnormality and are progressively depleted in HD (4, 12). Previous studies, however, have not resolved whether all populations of striatal projection neurons are equally affected in HD. The identification ofthe putative populations of striatal projection neurons that are earliest and most severely affected in HD, however, could provide valuable clues regarding the basis of striatal cell death in HD. To determine whether some populations of striatal proje...

We held an international consensus conference on frontotemporal dementia, behavioral disturbances, and parkinsonism linked to chromosome 17 to determine whether these are homogeneous or heterogeneous disorders, to agree on terminology, and to develop strategies for further research. The group identified 13 kindreds with sufficient evidence for linkage, finding in common to all a critical 2 cM between markers D17S791 and D17S800. There was agreement that (1) despite previous descriptions that have emphasized one or another clinical or neuropathological feature, the kindreds share clinical and neuropathological features; (2) until more specific information about the genetic defects becomes available, this disorder is best termed frontotemporal dementia and parkinsonism linked to chromosome 17; and (3) further research will be enhanced by identifying the gene or genes responsible for this disorder, detecting additional cases within known families and, in new families, correlating mutations with phenotypes and more fully delineating the clinical, neuropsychological, and neuropathological characteristics of this disorder.

Cells that took up tritiated thymidine (H-3T) at various periods of intrauterine and early infant life in the periventricdar proliferative zone and migrated to form the isocortex in the rat were tracked autoradiographically in series of stages to characterize their movements. Cells labeled at any stage soon separated themselves into cohorts, some continuing to proliferate, others migrating a t once, and still others delaying before migrating. Migratory cells moved to the developing cortex along the curved and oblique paths of the pallial fibers, whose basic plan was established by the early thalamocortical fibers. Magnitude of speed was 15 to 30 I.L per hour. The primitive neural cells that originated on each of the fourteenth to eighteenth intrauterine days first reached the cortex in about 48 hours, others took two or three days longer. Migrations originating on the nineteenth to twenty-first days continued into the week after birth; as the primitive cells approached the cortex, however, they differentiated into young neurons, and traveled perpendicularly to its outer part. The first cohort of twentieth day labeled cells reached their intracortical destinations in about three days, the last in about ten days. The isocortex was formed essentially from within outward. The first neuroglia destined for the isocortex arose on the twenty-first intrauterine day.

N-Methyl-D-aspartate (NMDA), phencyclidine (PCP), and quisqualate receptor binding were compared to benzodiazepine, gamma-aminobutyric acid (GABA), and muscarinic cholinergic receptor binding in the putamen and cerebral cortex of individuals with Huntington's disease (HD). NMDA receptor binding was reduced by 93 percent in putamen from HD brains compared to binding in normal brains. Quisqualate and PCP receptor binding were reduced by 67 percent, and the binding to other receptors was reduced by 55 percent or less. Binding to these receptors in the cerebral cortex was unchanged in HD brains. The results support the hypothesis that NMDA receptor-mediated neurotoxicity plays a role in the pathophysiology of Huntington's disease.

We report six demented individuals with pathologically verified diffuse Lewy body disease (DLBD) studied with fluoro-deoxyglucose positron emission tomography (FDG-PET). Three subjects had pure DLBD and three subjects had combined DLBD and Alzheimer's disease (DLBD-AD) pathology. FDG-PET revealed evidence of diffuse cerebral hypometabolism in both pure DLBD and DLBD-AD with marked declines in association cortices with relative sparing of subcortical structures and primary somatomotor cortex, a pattern reported previously in AD. Unlike AD, however, these subjects also had hypometabolism in the occipital association cortex and primary visual cortex. These findings indicate the presence of diffuse cortical abnormalities in DLBD and suggest that FDG-PET may be useful in discriminating DLBD from AD antemortem.