Involvement of precerebellar nuclei in Pick's disease

Pick's disease is a progressive degenerative disorder of the human brain which involves not only numerous areas of the cerebral cortex but also a characteristic set of subcortical nuclei. The disorder is associated with the formation of abnormal and hyperphosphorylated tau protein, which occurs in only a few susceptible neuronal types and leads to major cytoskeletal alterations. Preferentially affected by the destructive process are small nerve cells of both cortical areas and subcortical nuclei. Immunoreactions for abnormally phosphorylated tau protein permit identification of the alterations in their entirety. In an initial step in their development, patches of a nonargyrophilic material appear, irregularly filling both the somata and neurites of afflicted cells. The abnormal material is then partially converted into condensed spindle-shaped or spherical structures, which gradually become significantly argyrophilic. Globose argyrophilic Pick bodies eventually appear within the somata, and small Pick neurites of variable sizes and shapes develop in varicose expansions of the dendritic processes. Silver staining reveals only a fraction of the abnormal material and is adequate only for diagnostic purposes, while immunostaining of the abnormal tau protein discloses the complete neuropathological picture. The present study points to a conspicuous affliction of specific precerebellar nuclei in Pick's disease. Immunoreactive punctae, probably corresponding to terminal synaptic boutons of afferent fibers, appear at sites in the inferior olive receiving intense input from the cerebral cortex. The brunt of the changes, however, are borne by the pontine gray, the arcuate nucleus, the pontobulbar body, and the paramedian reticular nucleus. Altered areas show immunoreactive punctae and an abundance of small immunoreactive nerve cells partially containing Pick bodies and Pick neurites. Again, a feature common to all the affected nuclei is that they receive major input from the cerebral cortex, while other precerebellar nuclei with preponderant input from the spinal cord and/or other noncortical sources remain unscathed or exhibit only sparse involvement. The lesional pattern which develops in specific precerebellar nuclei is interpreted to be a partial reflection of the cortical involvement of Pick's disease.