@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 = "Funding Information: Acknowledgments: The authors thank those who contributed to their research, particularly the patients and families who donated DNA samples and brain tissue for this work. The Mayo Clinic Jacksonville is a Morris K. Udall Parkinson{\textquoteright}s Disease Research Center of Excellence (NINDS P50 NS072187). This work is also supported by NINDS R01 NS078086 (to O.A.R.), P01 NS44233 (to P.A.L.), U54 NS065736 (to P.A.L.), K23 NS075141 (to W.S.), UL1 RR24150 (to P.A.L.), R01 NS092625 (to P.A.L.), R01 FD478 (to P.A.L.), P50 AG016574 (to Alzheimer{\textquoteright}s Disease Research Center), U01 AG006786 (to Mayo Clinic Study of Aging), Mayo Clinic Center for Regenerative Medicine, Mayo Clinic Center for Individualized Medicine, Mayo Clinic Neuroscience Focused Research Team, Cure MSA Foundation, 17K14966 (to K.O.) from Grant-in-Aid for Young Scientists (B), and a gift from Carl Edward Bolch, Jr., and Susan Bass Bolch. C.L. is the recipient of a FRSQ postdoctoral fellowship and is a 2015 Younkin Scholar supported by the Mayo Clinic Alzheimer{\textquoteright}s Disease and Related Dementias Genetics program. Funding Information: The authors thank those who contributed to their research, particularly the patients and families who donated DNA samples and brain tissue for this work. The Mayo Clinic Jacksonville is a Morris K. Udall Parkinson's Disease Research Center of Excellence (NINDS P50 NS072187). This work is also supported by NINDS R01 NS078086 (to O.A.R.), P01 NS44233 (to P.A.L.), U54 NS065736 (to P.A.L.), K23 NS075141 (to W.S.), UL1 RR24150 (to P.A.L.), R01 NS092625 (to P.A.L.), R01 FD478 (to P.A.L.), P50 AG016574 (to Alzheimer's Disease Research Center), U01 AG006786 (to Mayo Clinic Study of Aging), Mayo Clinic Center for Regenerative Medicine, Mayo Clinic Center for Individualized Medicine, Mayo Clinic Neuroscience Focused Research Team, Cure MSA Foundation, 17K14966 (to K.O.) from Grant-in-Aid for Young Scientists (B), and a gift from Carl Edward Bolch, Jr., and Susan Bass Bolch. C.L. is the recipient of a FRSQ postdoctoral fellowship and is a 2015 Younkin Scholar supported by the Mayo Clinic Alzheimer's Disease and Related Dementias Genetics program. 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",
publisher = "John Wiley and Sons Inc.",
number = "4",
}