Widespread occurrence of α-synuclein/NACP-immunoreactive neuronal inclusions in juvenileand adult-onset Hallervorden–Spatz diseasewith Lewy bodies


Wakabayashi Brain Disease Research Center, Brain Research Institute, Niigata University, 1 Asahimachi, Niigata 951–8585, Japan.


α-Synuclein (originally called precursor of the non-Aβ component of Alzheimer’s disease amyloid-NACP) is a presynaptic nerve terminal protein and is now known to be a major component of Lewy bodies (LBs) in Parkinson’s disease. Previous studies have shown that LBs are occasionally found in patients with Hallervorden–Spatz disease (HSD), a hereditary or sporadic neuroaxonal dystrophy. Therefore, an immunocytochemical examination of the brain tissues from two patients with HSD for α-synuclein/NACP was performed. In both cases, LBs were observed in the substantia nigra, locus ceruleus and other subcortical nuclei. These LBs were strongly immunolabelled with anti-α-synuclein/NACP. Moreover, abnormal α-synuclein/NACP-immunoreactive structures in the neuronal somata and processes were found in the cerebral neocortex, hippocampus, basal ganglia, thalamus, pontine and inferior olivary nuclei, spinal grey matter, and peripheral sympathetic ganglia. Although numerous dystrophic axons (spheroids) were found throughout the brain, either none or only a few were positive for α-synuclein/NACP. These findings suggest that widespread accumulation of α-synuclein/NACP is a pathological feature in patients suffering from HSD with LBs, and that this phenomenon is unrelated to axonal spheroid formation.