α-Synuclein fibrils constitute the central core of oligodendroglial inclusion filaments in multiple system atrophy

Abstract

Multiple system atrophy (MSA) belongs to synucleinopathies and is characterized pathologically by oligodendroglial inclusions (GCIs) composed of 20- to 30-nm tubular filaments. α-Synuclein fibrils formed in vitro, however, range between 10 and 12 nm in diameter. To understand the relationship between α-synuclein and GCI filaments, we conducted structural analyses of GCIs in fixed brain sections and isolated from fresh-frozen MSA brains. In fixed brain sections, GCIs were composed of amorphous material-coated filaments up to 30 nm in size. The filaments were often organized in parallel bundles extending into oligodendroglial processes. In freshly isolated GCIs, progressive buffer washes remov..