Cerebellar involvement in Pick's disease: affliction of mossy fibers, monodendritic brush cells, and dentate projection neurons

Abstract

Pick's disease chiefly is characterized by progressive degeneration of specific telencephalic cortical areas and associated subcortical nuclei. Components of the cerebellum also are affected. Immunoreactions for abnormally hyperphosphorylated tau protein, indicating the development of cytoskeletal anomalies in a few susceptible neuroectodermal cell types, permit visualization and identification of the pathology. Initially, accumulations of nonargyrophilic material appear in the perikarya and cellular processes of susceptible nerve cells. In some neuronal types, the abnormal deposits are transformed into more condensed inclusions, so-called Pick bodies in perikarya and Pick neurites in cellular processes, some of which become argyrophilic in the course of the disease. This study employs silver techniques and immunoreactions to draw attention to Pick's disease-associated lesions in the cerebellar cortex and cerebellar nuclei. Immunoreactive rosettes, which correspond to the terminal synaptic boutons of mossy fibers, frequently are encountered in the cerebellar granule cell layer. Some cases of Pick's disease also exhibit afflicted monodendritic brush cells in this layer. Single immunopositive Purkinje cells occasionally are seen as well. The brunt of the alterations is borne by cerebellar subdivisions receiving dense input from the telencephalic cortex through the pontocerebellar pathway (neocerebellum). The dentate nucleus shows immunoreactive axons with numerous varicose thickenings which remain confined to the reaches of this band-like nuclear gray and probably represent collaterals of altered mossy fibers. A large number of the dentate projection cells also contain the abnormal material in the perikarya, as well as in all of the neuronal processes. Many of these cells develop spherical nonargyrophilic condensations of this material. Output of the neocerebellum is conveyed to extended territories of the telencephalic cortex via the dentate nucleus and thalamus. Therefore, all of the cerebellar territories which receive major input from and generate output chiefly to the telencephalic cortex (pontocerebellum or neocerebellum) are notably afflicted in Pick's disease. Other subdivisions with preponderant input from the spinal cord and/or other noncortical sources remain intact or else are only minimally involved. It is concluded that the pattern of cerebellar involvement reflects Pick's disease-associated neocortical destruction.