Significantly, αS has been implicated as a major component of the tubulofilamentous inclusions found in oligodendrocytes in multiple system atrophy known as glial cytoplasmic inclusions (GCIs).2,3,5,6,28 Multiple system atrophy consists of a syndrome complex with parkinsonism and a combination of cerebellar, autonomic, and gait abnormalities as well as variable cognitive decline. These disorders include Shy-Drager syndrome, striatonigral degeneration, and olivopontocerebellar atrophy, all of which are characterized by the presence of αS-immunoreactive GCIs throughout the neocortex, hippocampus, brainstem, spinal cord, and dorsal root ganglia. In addition, neurodegeneration with brain iron accumulation, type I (also referred to as adult neuroaxonal dystrophy or Hallervorden-Spatz syndrome), is a rare neurodegenerative disorder characterized clinically by parkinsonism, cognitive decline, cerebellar signs, and bulbar symptoms. Pathologically, iron deposition is found in the globus pallidus, red nucleus, SNpc, and dentate nucleus of the cerebellum, and axonal swellings known as spheroids are seen. In addition, both GCIs and LB-like neuronal cytoplasmic inclusions are seen in both cortical and subcortical structures. The spheroids, GCIs, and neuronal cytoplasmic inclusions are all easily detected by antibodies against αS.28,29 The αS component of brain regions with these lesions is largely found in the insoluble fractions, similar to the pattern of distribution seen in LB disorders. Furthermore, axonal lesions after traumatic brain injury also have been demonstrated recently to express αS.29 Besides the above-mentioned disorders, there are several other neurodegenerative diseases in which αS-immunoreactive lesions may contribute to the pathologic features seen in the disorder but may not be the major protein constituent of the lesion. For example, a subset of the Pick bodies within the dentate gyrus of the hippocampus in patients with Pick disease is strongly immunoreactive for αS; however, the major building block of Pick bodies appears to be tau protein.3,5,16 In addition, glial inclusions in amyotrophic lateral sclerosis also show αS immunoreactivity (J.E.G., V.M.-Y.L., J.Q.T., unpublished data, 1999).