Objective: The main objective of this study was to investigate if there are widespread white matter abnormalities in multiple system atrophy (MSA).

Background: MSA differs from other synucleinopathies in that α-synuclein accumulates in oligodendrocytes, giving rise to so-called glial cytoplasmic inclusions (CGIs) predominantly located in white matter. The widespread presence of CGIs and their downstream effects described in the experimental and neuropathological literature [1, 2] would be expected to compromise the integrity of white matter structure.

Methods: In vivo structural and diffusion magnetic resonance imaging were acquired on 26 MSA patients and 26 healthy controls. A refined whole brain approach encompassing both the deep white matter (major fiber tracts) and the superficial white matter (located at the boundary of the cortical gray matter) was applied. Imaging data were further collected on 23 PD patients. In contrast to MSA patients, PD patients were expected to show unaltered global white matter, since in PD α-synuclein accumulates primarily in neurons rather than oligodendrocytes.

Results: MSA but not PD patients had whole brain deep and superficial white matter diffusivity abnormalities (p<0.001). Additionally, in MSA patients, global deep and superficial white matter diffusivity was associated with both motor (UMSARS-II) and cognitive function (MMSE).

Conclusions: In the light of established neuropathological and experimental evidence, our observations suggest pervasive oligodendrocyte dysfunction in MSA. Furthermore, pervasive oligodendrocyte dysfunction likely underlies some of the clinical manifestations of MSA. Our findings provide a novel framework to investigate in vivo the mechanisms underlying this devastating disease and its potential remediation. This poster was previously presented at the 6th International MSA Congress held in New York March 1st-2nd 2018. NDC and OP share the first co-authorship on this work.

References: [1] Nykjaer CH, Brudek T, Salvesen L, Pakkenberg B. Changes in the cell population in brain white matter in multiple system atrophy. Mov Disord [Internet]. 2017;32(7):1074–1082. [2] Ettle B, Schlachetzki JCM, Winkler J. Oligodendroglia and Myelin in Neurodegenerative Diseases: More Than Just Bystanders? Mol Neurobiol [Internet]. 2017;53(5):3046–3062.

« Back to 2018 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/broad-white-matter-impairment-in-multiple-system-atrophy-a-case-for-oligodendrocyte-dysfunction/