Familial tauopathy mimicking corticobasal degeneration an autopsy study on three siblings.

ABSTRACT

We describe a family with tauopathy involving three autopsied siblings. All of the three siblings, as well as their grandmother, exhibited parkinsonism responsive to levodopa in one of the three, later associated with a possible reduction in spontaneity, compatible with frontal lobe dysfunction. Autopsy findings shared by the three siblings included, marked degeneration in the basal ganglia, especially in the substantia nigra and mild to moderate spongiosis in the cerebral cortices (mainly frontal) with achromatic neurons and tau/Gallyas-positive spherical aggregates resembling astrocytic plaques. Widespread deposition of tau in neurons, thread-like structures and oligodendrocytes as coiled body was robust in these lesions, whereas alpha-synuclein-positive deposits were absent. These features are compatible with sporadic corticobasal degeneration (CBD). Hippocampal neurons were characterized by its non-fibrillary tau deposits in the cytoplasm, as similarly visualized with Gallyas silver stain (Gal), while the Campbell-Switzer method (CS) failed to exhibit argyrophilia. This staining profile of neuronal cytoplasm with non-fibrillary structure (tau+/Gal+/CS-) is characteristic for tau-positive cortical neurons in CBD, distinct from typical neurofibrillary tangles of Alzheimer type, positive for both Gal and CS. Moreover, degenerative change was more evident in CA2 than in CA1, as noted in some cases of tauopathy with accumulation of 4-repeat tau such as CBD. This familial tauopathy can be classified as an extremely rare example of CBD based on the distribution of characteristic lesions and staining profiles of tau-deposits.