Multiple system atrophy and apolipoprotein E

被引：19

作者：

Ogaki, Kotaro ^{[1
]}

Martens, Yuka A. ^{[1
]}

Heckman, Michael G. ^{[2
]}

Koga, Shunsuke ^{[1
]}

Labbe, Catherine ^{[1
]}

Lorenzo-Betancor, Oswaldo ^{[1
]}

Wernick, Anna I. ^{[1
]}

Walton, Ronald L. ^{[1
]}

Soto, Alexandra I. ^{[1
]}

Vargas, Emily R. ^{[2
]}

Nielsen, Henrietta M. ^{[1
,3
]}

Fujioka, Shinsuke ^{[4
]}

Kanekiyo, Takahisa ^{[1
]}

Uitti, Ryan J. ^{[4
]}

van Gerpen, Jay A. ^{[4
]}

Cheshire, William P. ^{[4
]}

Wszolek, Zbigniew K. ^{[4
]}

Low, Phillip A. ^{[5
]}

Singer, Wolfgang ^{[5
]}

Dickson, Dennis W. ^{[1
]}

Bu, Guojun ^{[1
]}

Ross, Owen A. ^{[1
,6
,7
]}

机构：

[1] Mayo Clin Jacksonville, Dept Neurosci, 4500 San Pablo Rd, Jacksonville, FL 32224 USA

[2] Mayo Clin, Div Biomed Stat & Informat, Jacksonville, FL 32224 USA

[3] Stockholm Univ, Dept Neurochem, Stockholm, Sweden

[4] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA

[5] Mayo Clin, Dept Neurol, Rochester, MN USA

[6] Mayo Grad Sch, Neurobiol Dis, Jacksonville, FL USA

[7] Dept Clin Genom, Jacksonville, FL USA

来源：

MOVEMENT DISORDERS | 2018年 / 33卷 / 04期

关键词：

multiple system atrophy; apolipoprotein E; genetics; protection; oligodendrocyte; ALPHA-SYNUCLEIN; SUPRANUCLEAR PALSY; TAU; ASSOCIATION; DIAGNOSIS; APOE;

D O I：

10.1002/mds.27297

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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 -synuclein pathology, and also examined whether apolipoprotein E isoforms differentially affect -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 -synuclein and recombinant human apolipoprotein E, with internalized -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 2 or 4. -Synuclein burden was also not associated with Apolipoprotein E alleles in the pathologically confirmed patients. Interestingly, in our cell assays, apolipoprotein E 4 significantly reduced -synuclein uptake in the oligodendrocytic cell line. Conclusions: Despite differential effects of apolipoprotein E isoforms on -synuclein uptake in a human oligodendrocytic cell, we did not observe a significant association at the Apolipoprotein E locus with risk of MSA or -synuclein pathology. (c) 2018 International Parkinson and Movement Disorder Society

引用

页码：647 / 650

页数：4

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