Abstract
Glial cytoplasmic inclusions are the pathological hallmark of multiple system atrophy. However, the molecular mechanisms underlying the formation of glial cytoplasmic inclusions remain unclear. Ξ±βSynuclein, a major component of glial cytoplasmic inclusions, has the ability to interact with 14β3β3 proteins, which mediate several types of signal transduction pathways. To elucidate the role of these 14β3β3 proteins in patients with multiple system atrophy, we performed immunohistochemical studies on 14β3β3 in brain tissue specimens from 7 control subjects and from 15 patients with multiple system atrophy. In both control and multiple system atrophy cases, 14β3β3 immunoreactivity was observed mainly in the neuronal somata and proximal processes, as well as the nerve fibers. Even in the severely affected regions of patients with multiple system atrophy, 14β3β3 immunoreactivity generally was spared in the surviving neurons, some of which were strongly immunolabeled. In addition, numerous glial cytoplasmic inclusions were intensely immunostained, and neuronal cytoplasmic inclusions and dystrophic neurites were also immunoreactive for 14β3β3. Our results suggest that an aberrant accumulation of 14β3β3 proteins may occur in brains affected by multiple system atrophy, and that 14β3β3 proteins may be associated with the pathogenesis of multiple system atrophy. Ann Neurol 2002;52:000β000