Corticobasal degeneration with focal, massive tau accumulation in the subcortical white matter astrocytes.
We report two sporadic cases of tauopathy with unusual neuropathological features. The ages of the patients at death were 86 and 74 years, and the disease durations were 4 and 3 years, respectively. The former patient showed progressive dementia and amyotrophy (autopsy revealed that severe cervical spondylosis was responsible for the amyotrophy), and the latter showed progressive parkinsonism and dementia. The essential brain pathologies were similar to each other; although ballooned neurons and astrocytic tau lesions (astrocytic plaques) were present in the affected cerebral cortex, the most striking finding was focal, much heavier accumulation of tau in the subcortical white matter. Moreover, double-labeling immunostaining, as well as Gallyas-Braak electron and AT8 immunoelectron microscopic studies strongly suggested that in the affected subcortical white matter, the accumulation of tau occurred mainly in the astrocytic processes. In the latter patient, for whom frozen brain tissue was available, immunoblotting of insoluble tau revealed a pattern compatible with that obtained from brain affected by typical corticobasal degeneration (CBD), and gene analysis of tau revealed no mutations, with a H1 haplotype. Finally, in both cases, the pathological diagnosis of CBD was considered to be appropriate. However, the tau pathology affecting the subcortical white matter astrocytes was very unusual for the disease.