Morphological Purkinje cell changes in spinocerebellar ataxia type 6

Spinocerebellar ataxia type 6 (SCA6) was recently identified as a form of a utosomal dominant spinocerebellar ataxia associated with a small CAG repeat expansion of the gene encoding an alpha 1 A-voltage-dependent calcium chan nel gene subunit on chromosome 19p13. In this study 50-mu m-thick sections of cerebellar tissue from one patient with SCAB were subjected to free-floa ting immunohistochemical staining with calbindin-D and parvalbumin antibodi es. Severe loss of Purkinje cells was found, particularly in the vermis, an d various morphological changes in Purkinje cells and their dendritic arbor izations were demonstrated. Many of the remaining Purkinje cells were found to have heterotopic, irregularly shaped nuclei, an unclear cytoplasmic mem brane outline, and somatic sprouts. Increased numbers of spine-like protrus ions from swelling dendritic arborizations were found in the molecular laye r. The axonal arrangement was disordered, and many torpedos were found in t he granular layer and white matters. These morphological changes are comple tely different from those observed in paraneoplastic cerebellar degeneratio n (PCD) and multiple system atrophy (MSA) and are considered to be related to the genetic abnormality that causes abnormal development of Purkinje cel ls.