Multiple system atrophy and apolipoprotein E
Open accessAbstract
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
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No association has been found between the APOE genotype and a primary neuropathological diagnosis of multiple system atrophy.
“By contrast, no association has been found between the APOE genotype and a primary neuropathological diagnosis of multiple system atrophy67,74.”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [74]
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Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · see citing works
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Research works printed but not linked: 16
- [1]Gilman S Wenning GK Low PA Second consensus statement on the diagnosis of multiple system atrophy Neurology 2008 71 9 670 676 18725592 PMC2676993
- [2]Bleasel JM Wong JH Halliday GM Kim WS Lipid dysfunction and pathogenesis of multiple system atrophy Acta Neuropathol Commun 2014 2 15 24502382 PMC3922275
- [3]Liu CC Kanekiyo T Xu H Bu G Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy Nat Rev Neurol 2013 9 2 106 118 23296339 PMC3726719
- [4]Federoff M Schottlaender LV Houlden H Singleton A Multiple system atrophy: the application of genetics in understanding etiology Clin Auton Res 2015 25 1 19 36 25687905 PMC5217460
- [5]Trojanowski JQ Revesz T Neuropathology Working Group on MSA Proposed neuropathological criteria for the post mortem diagnosis of multiple system atrophy Neuropathol Appl Neurobiol 2007 33 6 615 620 17990994
- [6]Dickson DW Liu W Hardy J Widespread alterations of alpha-synuclein in multiple system atrophy The American journal of pathology 1999 155 4 1241 1251 10514406 PMC1867032
- [7]Koga S Ono M Sahara N Higuchi M Dickson DW Fluorescence and autoradiographic evaluation of tau PET ligand PBB3 to alpha-synuclein pathology Mov Disord 2017 32 6 884 892 28440890 PMC5577807
- [9]Thal DR Rub U Orantes M Braak H Phases of A beta-deposition in the human brain and its relevance for the development of AD Neurology 2002 58 12 1791 1800 12084879
- [10]Cairns NJ Atkinson PF Kovacs T Lees AJ Daniel SE Lantos PL Apolipoprotein E e4 allele frequency in patients with multiple system atrophy Neurosci Lett 1997 221 2–3 161 164 9121689
- [11]Morris HR Schrag A Nath U Effect of ApoE and tau on age of onset of progressive supranuclear palsy and multiple system atrophy Neurosci Lett 2001 312 2 118 120 11595348
- [12]Morris HR Vaughan JR Datta SR Multiple system atrophy/progressive supranuclear palsy: alpha-Synuclein, synphilin, tau, and APOE Neurology 2000 55 12 1918 1920 11134398
- [13]Toji H Kawakami H Kawarai T No association between apolipoprotein E alleles and olivopontocerebellar atrophy Journal of the neurological sciences 1998 158 1 110 112 9667788
- [14]Josephs KA Tsuboi Y Cookson N Watt H Dickson DW Apolipoprotein E epsilon 4 is a determinant for Alzheimer-type pathologic features in tauopathies, synucleinopathies, and frontotemporal degeneration Archives of neurology 2004 61 10 1579 1584 15477512
- [15]Sailer A Scholz SW Nalls MA A genome-wide association study in multiple system atrophy Neurology 2016 87 15 1591 1598 27629089 PMC5067544
- [16]Gan-Or Z Montplaisir JY Ross JP The dementia-associated APOE epsilon4 allele is not associated with rapid eye movement sleep behavior disorder Neurobiology of aging 2017 49 218e213 218.e215 27814994
- [17]Kisos H Pukass K Ben-Hur T Richter-Landsberg C Sharon R Increased neuronal alpha-synuclein pathology associates with its accumulation in oligodendrocytes in mice modeling alpha-synucleinopathies PloS one 2012 7 10 e46817 23077527 PMC3471961
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α-synuclein in the pathophysiology of Alzheimer’s disease
Twohig, D., & Nielsen, H. M. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0320-x · Cited by 374 · see citing works
Self-citationMultifaceted roles of APOE in Alzheimer disease
Jackson, R. J., Hyman, B. T., & Serrano-Pozo, A. (2024) · Nature Reviews Neurology · doi:10.1038/s41582-024-00988-2 · Cited by 193 · see citing works
The relevance of cerebrospinal fluid α-synuclein levels to sporadic and familial Alzheimer’s disease
for the Dominantly Inherited Alzheimer Network (DIAN), Twohig, D., Rodriguez-Vieitez, E., Sando, S. B., Berge, G., Lauridsen, C., Møller, I., Grøntvedt, G. R., Bråthen, G., Patra, K., et al. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0624-z · Cited by 68 · see citing works
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- Authors
- Ogaki, K., Martens, Y. A., Heckman, M. G., Koga, S., Labbé, C., Lorenzo‐Betancor, O., Wernick, A. I., Walton, R. L., Soto, A. I., Vargas, E. R., Nielsen, H. M., Fujioka, S., Kanekiyo, T., Uitti, R. J., van Gerpen, J. A., Cheshire, W. P., Wszolek, Z. K., Low, P. A., Singer, W., Dickson, D. W., Bu, G., & Ross, O. A.
- Affiliations
- Mayo Clinic (US)
- Department of Neurology Mayo Clinic Jacksonville Florida USA
- Corresponding author
- Ross, Owen A.
- ORCID
- Martens, Yuka A.
- Heckman, Michael G.
- Koga, Shunsuke
- Labbé, Catherine
- Lorenzo‐Betancor, Oswaldo
- Wernick, Anna I.
- Vargas, Emily R.
- Nielsen, Henrietta M.
- Fujioka, Shinsuke
- Kanekiyo, Takahisa
- Uitti, Ryan J.
- Cheshire, William P.
- Wszolek, Zbigniew K.
- Low, Phillip A.
- Singer, Wolfgang
- Dickson, Dennis W.
- Bu, Guojun
- Ross, Owen A.
- Venue
- Movement Disorders
- Publisher
- Wiley
- Published
- 2018-02-14
- Volume
- 33
- Issue
- 4
- Pages
- 647-650
- ISSN
- 0885-3185 (ISSN-L)
- 1531-8257
- PMC
- PMC5889322
- OpenAlex
- W2791432510
- Cited by
- 24
- References
- 1
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2022: 4 · 2021: 1 · 2020: 4 · 2019: 4 · 2018: 2
- FWCI
- 1.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Movement Disorders (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Funders
- NINDS (P50 NS072187, R01 NS078086, P01 NS44233, U54 NS065736, K23 NS075141, UL1 RR24150, R01 NS092625, R01 FD478, P50 AG016574, P01‐AG003949, U01 AG006786)
- National Institute of Neurological Disorders and Stroke (R01NS082565, R21NS082888)
- Michael J. Fox Foundation for Parkinson's Research
- Alzheimer's Association (2015‐NIRG‐339824)
- Boston Scientific Corporation
- Cure Alzheimer's Fund (RF1AG051504, R01AG027924, R01AG035355, R01AG046205, P01NS074969)
- U.S. Department of Defense (W81XWH‐17‐1‐0249, U54 NS100693)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- multiple system atrophy, apolipoprotein E, alpha-synuclein, oligodendrocytes, myelin, genetic association, apolipoprotein E isoforms, neurodegeneration, lipid metabolism
- MeSH terms
- Aged, Apolipoproteins E, Astrocytes, Cell Line, Transformed, Female, Genetic Testing, Genotype, Humans, Male, Multiple System Atrophy, alpha-Synuclein
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