Session Information
Date: Sunday, October 7, 2018
Session Title: Parkinsonism, MSA, PSP (Secondary and Parkinsonism-Plus)
Session Time: 1:45pm-3:15pm
Location: Hall 3FG
Objective: This study evaluated genetic associations of Apolipoprotein E alleles with risk of multiple system atrophy (MSA) and α-synuclein pathology, and also examined whether apolipoprotein E isoforms differentially affect α-synuclein uptake in a oligodendrocyte cell.
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.
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.
To cite this abstract in AMA style:
K. Ogaki, Y. Martens, M. Heckman, S. Koga, L. Labbé, O. Lorenzo-Betancor, A. Wernick, R. Walton, A. Soto, E. Vargas, H. Nielsen, S. Fujioka, T. Kanekiyo, R. Uitti, J. van Gerpen, W. Cheshire, Z. Wszolek, P. Low, W. Singer, N. Hattori, D. Dickson, G. Bu, O. Ross. Apolipoprotein E and multiple system atrophy [abstract]. Mov Disord. 2018; 33 (suppl 2). https://www.mdsabstracts.org/abstract/apolipoprotein-e-and-multiple-system-atrophy/. Accessed September 7, 2024.« Back to 2018 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/apolipoprotein-e-and-multiple-system-atrophy/