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. 2018 Apr;33(4):647-650.
doi: 10.1002/mds.27297. Epub 2018 Feb 14.

Multiple system atrophy and apolipoprotein E

Kotaro Ogaki  1 , Yuka A Martens  1 , Michael G Heckman  2 , Shunsuke Koga  1 , Catherine Labbé  1 , Oswaldo Lorenzo-Betancor  1 , Anna I Wernick  1 , Ronald L Walton  1 , Alexandra I Soto  1 , Emily R Vargas  2 , Henrietta M Nielsen  1   3 , Shinsuke Fujioka  4 , Takahisa Kanekiyo  1 , Ryan J Uitti  4 , Jay A van Gerpen  4 , William P Cheshire  4 , Zbigniew K Wszolek  4 , Phillip A Low  5 , Wolfgang Singer  5 , Dennis W Dickson  1 , Guojun Bu  1 , Owen A Ross  1   6   7
Affiliations

Multiple system atrophy and apolipoprotein E

Kotaro Ogaki et al. Mov Disord. 2018 Apr.

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. © 2018 International Parkinson and Movement Disorder Society.

Keywords: apolipoprotein E; genetics; multiple system atrophy; oligodendrocyte; protection.

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Figures

Figure 1
Figure 1. ApoE4 reduces α-Synuclein uptake by oligodendrocytic cell line
(A) Confocal analysis of α-Synuclein (green) internalization by MO3.13 co-treated with apoE or BSA. Blue: DAPI, red: LysoTracker®. Scale bar= 20 μm. (B) Flow cytometry analysis of MO3.13 incubated with α-Synuclein and apoE (E2: green, E3: blue, E4: red) or BSA (purple). (C) The median fluorescence signals in each condition. Data plotted as mean ± SD (N= 4, One-Way ANOVA with Tukey’s post-hoc analysis, * p< 0.05, ** p< 0.01).
See this image and copyright information in PMC

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