Multiple system atrophy and apolipoprotein E

Kotaro Ogaki, Yuka A. Martens, Michael G. Heckman, Shunsuke Koga, Catherine Labbé, Oswaldo Lorenzo-Betancor, Anna I. Wernick, Ronald L. Walton, Alexandra I. Soto, Emily R. Vargas, Henrietta M. Nielsen, Shinsuke Fujioka, Takahisa Kanekiyo, Ryan J. Uitti, Jay A. van Gerpen, William P. Cheshire, Zbigniew K. Wszolek, Phillip A. Low, Wolfgang Singer, Dennis W. DicksonGuojun Bu, Owen A. Ross

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Background: Dysregulation of the specialized lipid metabolism involved in myelin synthesis and maintenance by oligodendrocytes has been associated with the unique neuropathology of MSA. We hypothesized that apolipoprotein E, which is associated with neurodegeneration, may also play a role in the pathogenesis of MSA. Objective: This study evaluated genetic associations of Apolipoprotein E alleles with risk of MSA and α-synuclein pathology, and also examined whether apolipoprotein E isoforms differentially affect α-synuclein uptake in a oligodendrocyte cell. Methods: One hundred sixty-eight pathologically confirmed MSA patients, 89 clinically diagnosed MSA patients, and 1,277 control subjects were genotyped for Apolipoprotein E. Human oligodendrocyte cell lines were incubated with α-synuclein and recombinant human apolipoprotein E, with internalized α-synuclein imaged by confocal microscopy and cells analyzed by flow cytometry. Results: No significant association with risk of MSA or was observed for either Apolipoprotein E ɛ2 or ɛ4. α-Synuclein burden was also not associated with Apolipoprotein E alleles in the pathologically confirmed patients. Interestingly, in our cell assays, apolipoprotein E ɛ4 significantly reduced α-synuclein uptake in the oligodendrocytic cell line. Conclusions: Despite differential effects of apolipoprotein E isoforms on α-synuclein uptake in a human oligodendrocytic cell, we did not observe a significant association at the Apolipoprotein E locus with risk of MSA or α-synuclein pathology.

Original languageEnglish (US)
Pages (from-to)647-650
Number of pages4
JournalMovement Disorders
Volume33
Issue number4
DOIs
StatePublished - Apr 2018

Keywords

  • apolipoprotein E
  • genetics
  • multiple system atrophy
  • oligodendrocyte
  • protection

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Fingerprint Dive into the research topics of 'Multiple system atrophy and apolipoprotein E'. Together they form a unique fingerprint.

  • Cite this

    Ogaki, K., Martens, Y. A., Heckman, M. G., Koga, S., Labbé, C., Lorenzo-Betancor, O., Wernick, A. I., Walton, R. L., Soto, A. I., Vargas, E. R., Nielsen, H. M., Fujioka, S., Kanekiyo, T., Uitti, R. J., van Gerpen, J. A., Cheshire, W. P., Wszolek, Z. K., Low, P. A., Singer, W., ... Ross, O. A. (2018). Multiple system atrophy and apolipoprotein E. Movement Disorders, 33(4), 647-650. https://doi.org/10.1002/mds.27297