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Multiple system atrophy and apolipoprotein E
Author(s) -
Ogaki Kotaro,
Martens Yuka A.,
Heckman Michael G.,
Koga Shunsuke,
Labbé Catherine,
LorenzoBetancor Oswaldo,
Wernick Anna I.,
Walton Ronald L.,
Soto Alexandra I.,
Vargas Emily R.,
Nielsen Henrietta M.,
Fujioka Shinsuke,
Kanekiyo Takahisa,
Uitti Ryan J.,
van Gerpen Jay A.,
Cheshire William P.,
Wszolek Zbigniew K.,
Low Phillip A.,
Singer Wolfgang,
Dickson Dennis W.,
Bu Guojun,
Ross Owen A.
Publication year - 2018
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.27297
Subject(s) - apolipoprotein b , apolipoprotein e , oligodendrocyte , biology , neurodegeneration , neuropathology , myelin , medicine , pathology , endocrinology , central nervous system , disease , cholesterol
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. © 2018 International Parkinson and Movement Disorder Society