CORTICOBASAL DEGENERATION - NEUROPATHOLOGIC AND CLINICAL HETEROGENEITY

We investigated clinical and neuropathologic heterogeneity and apolipo protein E (apoE) genotype in 11 cases of neuropathologically diagnosed corticobasal degeneration (CBD). Although seven of the 11 patients pr esented with unilateral limb dysfunction, the remaining four patients had less typical presentations including memory loss, behavioral chang es, and difficulties with speech or gait. All 11 patients eventually d eveloped extrapyramidal signs as well as cortical features, most commo nly apraxia. At autopsy, the brains of seven of the 11 patients exhibi ted predominant neuronal loss and gliosis of perirolandic cortex; dege neration of more rostral frontal cortex was observed in three of the f our patients with atypical clinical presentations. All cases displayed ballooned neurons, tau-positive neuronal and glial inclusions, thread s and grains, and nigral degeneration. Six of the 11 cases manifested overlapping neuropathologic features of one or more disorders, includi ng Alzheimer's disease (AD), progressive supranuclear palsy (PSP), Par kinson's disease (PD), and hippocampal sclerosis. Interestingly, these six patients all exhibited memory loss early in the course of their i llness. The 11 CBD cases exhibited increased frequency (0.32) of the e psilon 4 allele of apoE, relative to control populations; the frequenc y remained elevated (0.25) even when the three cases with concomitant AD were excluded. Beta-amyloid (A beta) deposition in hippocampus or c ortex was present in five of the seven cases with an epsilon 4 genotyp e. These observations indicate that CBD is a pathologically and clinic ally heterogeneous disorder with substantial overlap with other neurod egenerative disorders.