What are glial cytoplasmic inclusions (GCIs) in patients with multiple system atrophy (MSA)?

Updated: Sep 24, 2018
  • Author: Stephen M Bloomfield, MD; Chief Editor: Selim R Benbadis, MD  more...
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Ultrastructural studies of GCIs with electron microscopy and monoclonal antibody probes have confirmed their location in oligodendroglial cells and revealed them to be composed of ubiquitin, tau, microtubule-associated protein-5, cyclin-dependent kinase 5 (cdk5), mitogen-activated protein kinase (MAPK), and alpha synuclein. The tau component in GCIs appears to be immunologically distinct from the tau protein found in patients with Alzheimer disease, PSP, or corticobasal degeneration (CBD). MAPK and cdk5 are usually found in neurons and not oligodendroglial cells. Phosphorylation of these microtubular proteins of the cytoskeleton by these aberrantly located or expressed protein kinases may lead to the formation of GCIs.

Other neuronal inclusions have been observed in both the cytoplasm and nucleus of both oligodendroglial cells and neurons in patients with MSA. However, these findings are seen less commonly than GCIs, which remain the hallmark lesion of MSA. The density of GCIs appears to correlate with the severity of oligodendroglial degeneration and not with the potential degeneration of axons or neurons.

The finding of GCIs within oligodendroglial cells of patients with MSA has led to a shift in research interest from neurons to glial cells in patients with various neurodegenerative disorders. A variety of cellular alterations in glial cells of patients with various neurodegenerative disorders has been described. However, none have resembled GCIs, and the clinical significance of these markers remains unclear. Further research in glial pathology may help uncover the pathophysiology in patients with neurodegenerative disorders.

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