As the eosinophilic structure (appearing pale pink) surrounding condensed Purkinje cell bodies (appearing dark

pink) was reminiscent of the halo in Lewy bodies, we named this peculiar change as, “halo-like amorphous materials”. Following our report of this peculiar Purkinje cell change, nearly 10 patients have been so far reported to show similar morphological changes in Purkinje cells.6 All the patients in who genetic tests for 16q-ADCA were performed harbored the same single-nucleotide C-to-T (−16 C > T) change in the puratrophin-1 gene specific to 16q-ADCA.7 learn more Therefore, making the diagnosis of 16q-ADCA among numbers of cerebellar degenerations seemed to become feasible based on this neuropathologic hallmark, “halo-like amorphous materials”. We next studied the halo-like amorphous materials immunohistologically

to clarify what are the components of this peculiar change.4,5 First, we studied the cytosolic calcium binding protein calbindin D28k, which is expressed exclusively in Purkinje cells in the cerebellum. On immunohistochemistry for calbindin D28k, we observed various morphological changes of Purkinje cells. For example, numerous somatic sprouts selleck chemical stemming from a Purkinje cell body was occasionally seen (Fig. 3a). In such cases, a zone with calbindin D28k immunoreactivity appeared corresponding to the halo-like amorphous materials. On other occasions, calbindin D28k immunoreactive “granules” were found outside Purkinje cells (Fig. 3b,c). Sometimes, calbindin D28k immunoreactive puncta appeared to create a zone surrounding the Purkinje cell body, suggesting that remnants of somatic sprouts constitute at least a part of halo-like

amorphous materials (Fig. 3b). Calbindin D28k-positive granules were also found distant from the Purkinje cells even though the halo-like amorphous materials themselves did not show obvious immunoreactivity against calbindin D28k (Fig. 3d). From these observations, we considered that the somatic sprouts from Purkinje cells are among the important constituents of the halo-like amorphous materials. We next studied synaptic proteins since Purkinje cells are known to receive synaptic inputs from various types of neurons. For this purpose we studied synaptophysin, OSBPL9 one of the pre-synaptic vesicle proteins. The numbers of synaptophysin-immunoreactive granules attaching to Purkinje cell bodies were not increased in SCA6 brains used as controls. On the other hand, such granules were remarkably increased in number in 16q-ADCA, creating a zone of synaptophysin-immunoractive structures surrounding Purkinje cell bodies (Fig. 4a). Such increased zones sometimes even extended up to the primary shaft of the Purkinje cell dendrites (Fig. 4b). This clearly added increased presynaptic terminals, conceivably originating from neurons other than Purkinje cells, as an important component of halo-like amorphous materials.