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The pathological process affects central autonomic, striatonigral, and olivopontocerebellar systems. These show varying degrees of neurodegeneration and underlie the stratification of the heterogenous disorder into MSA\u2010P and MSA\u2010C clinical variants, which correlate to the morphologic phenotypes of striatonigral degeneration and olivopontocerebellar atrophy (MSA\u2010C). The lesions are not limited to these most consistently and severely affected systems but may involve many other parts of the central, peripheral, and autonomic nervous systems, underpinning the multisystem character of MSA. The histological core feature are glial cytoplasmic inclusions (GCIs, Papp\u2010Lantos bodies) in all types of oligodendroglia that contain aggregates of misfolded \u03b1\u2010Synuclein (\u03b1\u2010Syn). In addition to the ectopic appearance of \u03b1\u2010Syn in oligodendrocytes and other cells, oxidative stress, proteasomal and mitochondrial dysfunction, excitotoxiciy, neuroinflammation, metabolic changes, and energy failure are important contributors to the pathogenesis of MSA, as shown by various neurotoxic and transgenic animal models. Although the basic mechanisms of \u03b1\u2010Syn\u2013triggered neurodegeneration are not completely understood, neuron\u2010to\u2010oligodendrocyte transfer of \u03b1\u2010Syn by prion\u2010like spreading, inducing oligodendroglial and myelin dysfunction associated with chronic neuroinflammation, are suggested finally to lead to a system\u2010specific pattern of neurodegeneration. \u00a9 2014 International Parkinson and Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.26052","type":"journal-article","created":{"date-parts":[[2014,10,9]],"date-time":"2014-10-09T03:18:08Z","timestamp":1412824688000},"page":"1720-1741","source":"Crossref","is-referenced-by-count":175,"title":["Neuropathology of multiple system atrophy: New thoughts about pathogenesis"],"prefix":"10.1002","volume":"29","author":[{"given":"Kurt A.","family":"Jellinger","sequence":"first","affiliation":[{"name":"Institute of Clinical Neurobiology Vienna 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