UBIQUITIN-POSITIVE ACHROMATIC NEURONS IN CORTICOBASAL DEGENERATION

A 66-year-old woman presented with an alien limb syndrome without deme ntia. The course of her illness was unremitting and at autopsy 6 years later her diagnosis was confirmed as corticobasal degeneration withou t Alzheimer-type pathology Although the presence of ballooned achromat ic cortical neurons and cell loss from the substantia nigra distinguis hes such patients, the site and density of achromatic neurons has not previously been quantified. We show that immunohistochemistry for the cell stress protein ubiquitin selectively stains these achromatic neur ons, whereas they do not stain for abnormally phosphorylated tau prote in. Phosphorylated neurofilament antibodies recognise both ballooned a nd non-ballooned neurons. In this case, high densities of ubiquitin-po sitive ballooned neurons were found in frontal cortical regions with t he highest densities in layers V and VI of the anterior cingulate cort ex. In addition, high densities of ubiquitin-positive ballooned neuron s were found in the insular cortex, claustrum and amygdala. These resu lts confirm past reports of frontal pathology, but show that there is also considerable pathology in insular and parahippocampal cortical re gions and some subcortical regions. Our findings suggest that the dist ribution and staining characteristics of ballooned neurons in corticob asal degeneration may help to differentiate these cases pathologically , while the absence of dementia appears to be an important clinical cr iterion.