Abstract
BackgroundThe histological hallmark of multiple system atrophy (MSA) is the presence of filamentous aggregations of phosphorylated α-synuclein in oligodendrocytes, referred to as glial cytoplasmic inclusions (GCIs). Although GCIs can occur widely in the central nervous system, accumulation of phosphorylated α-synuclein in Schwann cells has not been reported in MSA. We immunohistochemically examined the cranial and spinal nerves, peripheral ganglia and visceral autonomic nervous system of patients with MSA (n = 14) and control subjects (n = 20).ResultsIn MSA, accumulation of phosphorylated α-synuclein was found in the cytoplasm of Schwann cells. These Schwann cell cytoplasmic inclusions (SCCIs) were also immunopositive for ubiquitin and p62. SCCIs were found in 12 of 14 patients with MSA (85.7 %). They were most frequent in the anterior nerve of the sacral cord and, to a lesser extent, in the cranial nerves (oculomotor, glossopharyngeal-vagus and hypoglossal nerves), and spinal and sympathetic ganglia. SCCIs were rarely found in the visceral organs. Immunoelectron microscopy demonstrated that the SCCIs consisted of abnormal filaments, 15–20 nm in diameter. No such inclusions were found in controls.ConclusionThe present findings indicate that Schwann cells are also involved in the disease process of MSA.
Highlights
Multiple system atrophy (MSA) is an adult-onset neurodegenerative disorder manifested clinically as a combination of parkinsonism, cerebellar ataxia and autonomic dysfunction
The immunostaining with two monoclonal anti-phosphorylated α-synuclein antibodies and a monoclonal anti-aggregated α-synuclein antibody revealed Schwann cell cytoplasmic inclusions (SCCIs) in the cranial and spinal nerves, peripheral ganglia and visceral autonomic nervous system of multiple system atrophy (MSA) patients (Fig. 1a–q)
glial cytoplasmic inclusions (GCIs) appeared argyrophilic with the modified Gallyas-Braak method, whereas SCCIs were stained only weakly or partially (Fig. 1 t, u)
Summary
Multiple system atrophy (MSA) is an adult-onset neurodegenerative disorder manifested clinically as a combination of parkinsonism, cerebellar ataxia and autonomic dysfunction. We immunohistochemically examined the cranial and spinal nerves, peripheral ganglia and visceral autonomic nervous system of patients with MSA using antibodies against phosphorylated α-synuclein, and report for the first time that Schwann cells in these patients are affected by filamentous aggregations of phosphorylated α-synuclein. The histological hallmark of multiple system atrophy (MSA) is the presence of filamentous aggregations of phosphorylated α-synuclein in oligodendrocytes, referred to as glial cytoplasmic inclusions (GCIs). GCIs can occur widely in the central nervous system, accumulation of phosphorylated α-synuclein in Schwann cells has not been reported in MSA. We immunohistochemically examined the cranial and spinal nerves, peripheral ganglia and visceral autonomic nervous system of patients with MSA (n = 14) and control subjects (n = 20)
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