期刊
MOVEMENT DISORDERS
卷 33, 期 4, 页码 647-650出版社
WILEY
DOI: 10.1002/mds.27297
关键词
multiple system atrophy; apolipoprotein E; genetics; protection; oligodendrocyte
资金
- NINDS [P50 NS072187, R01 NS078086, P01 NS44233, U54 NS065736, K23 NS075141, UL1 RR24150, R01 NS092625, R01 FD478, P50 AG016574, U01 AG006786]
- Mayo Clinic Center for Regenerative Medicine
- Mayo Clinic Center for Individualized Medicine
- Mayo Clinic Neuroscience Focused Research Team
- Cure MSA Foundation [17K14966]
- FRSQ postdoctoral fellowship
- Mayo Clinic Alzheimer's Disease and Related Dementias Genetics program
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
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