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. Dickson; Guojun Bu; Owen A. Ross

doi:10.1002/mds.27297

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 journal › Article › peer-review

8 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 language	English (US)
Pages (from-to)	647-650
Number of pages	4
Journal	Movement Disorders
Volume	33
Issue number	4
DOIs	https://doi.org/10.1002/mds.27297
State	Published - Apr 2018

Keywords

apolipoprotein E
genetics
multiple system atrophy
oligodendrocyte
protection

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.1002/mds.27297

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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

Ogaki, K, Martens, YA, Heckman, MG, Koga, S, Labbé, C, Lorenzo-Betancor, O, Wernick, AI, Walton, RL, Soto, AI, Vargas, ER, Nielsen, HM, Fujioka, S, Kanekiyo, T, Uitti, RJ, van Gerpen, JA, Cheshire, WP, Wszolek, ZK , Low, PA , Singer, W , Dickson, DW , Bu, G & Ross, OA 2018, 'Multiple system atrophy and apolipoprotein E', Movement Disorders, vol. 33, no. 4, pp. 647-650. https://doi.org/10.1002/mds.27297

@article{44d07b961ebc4c7e84a06567b95ac712,

title = "Multiple system atrophy and apolipoprotein E",

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.",

keywords = "apolipoprotein E, genetics, multiple system atrophy, oligodendrocyte, protection",

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

note = "Publisher Copyright: {\textcopyright} 2018 International Parkinson and Movement Disorder Society",

year = "2018",

month = apr,

doi = "10.1002/mds.27297",

language = "English (US)",

volume = "33",

pages = "647--650",

journal = "Movement Disorders",

issn = "0885-3185",

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T1 - Multiple system atrophy and apolipoprotein E

AU - Ogaki, Kotaro

AU - Martens, Yuka A.

AU - Heckman, Michael G.

AU - Koga, Shunsuke

AU - Labbé, Catherine

AU - Lorenzo-Betancor, Oswaldo

AU - Wernick, Anna I.

AU - Walton, Ronald L.

AU - Soto, Alexandra I.

AU - Vargas, Emily R.

AU - Nielsen, Henrietta M.

AU - Fujioka, Shinsuke

AU - Kanekiyo, Takahisa

AU - Uitti, Ryan J.

AU - van Gerpen, Jay A.

AU - Cheshire, William P.

AU - Wszolek, Zbigniew K.

AU - Low, Phillip A.

AU - Singer, Wolfgang

AU - Dickson, Dennis W.

AU - Bu, Guojun

AU - Ross, Owen A.

PY - 2018/4

Y1 - 2018/4

N2 - 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.

AB - 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.

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JO - Movement Disorders

JF - Movement Disorders

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ER -

Multiple system atrophy and apolipoprotein E

Abstract

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