AIMS: Spinocerebellar ataxia type 3 (SCA3) is an inherited spinocerebellar 
ataxia caused by the expansion of trinucleotide CAG repeats in the gene encoding 
ataxin-3. The clinical manifestations of SCA3 include peripheral neuropathy, 
which is an important cause of disability in a subset of patients. Although the 
loss of neurones in the dorsal root ganglion (DRG) has been postulated to be the 
cause of this neuropathy, the precise mechanism remains to be elucidated.
METHODS: To clarify the clinicopathological characteristics of SCA3-associated 
peripheral neuropathy, we performed nerve conduction studies and 
histopathological analyses. Nerve conduction studies were carried out in 18 SCA3 
patients. Immunohistochemical analyses of the anterior and posterior roots of 
the spinal cord and peripheral nerves were performed in five SCA3 patients. We 
also employed immunohistochemistry and immunoelectron microscopy analyses with 
an anti-polyglutamine antibody.
RESULTS: The mean sensory nerve action potentials of the SCA3 patients were half 
of the normal values. The motor conduction velocities were decreased, and the 
distal latencies were also significantly prolonged in the nerves studied 
relative to the those in normal controls. Histopathological analyses detected 
axonal sprouting and myelin thinning in all cases. Ataxin-3 aggregates were 
found in the cytoplasm of Schwann cells in all of the SCA3 patients examined but 
not in control subjects.
CONCLUSIONS: In addition to the previously reported neuronopathy, the results of 
the present study indicate that Schwann cells are involved in the formation of 
the pathogenic intracytoplasmic ataxin-3 protein aggregates in patients with 
SCA3-associated neuropathy.