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dc.contributor.authorMoon, Hee-Jung
dc.contributor.authorHaroutunian, Vahram
dc.contributor.authorZhao, Liqin
dc.date.accessioned2023-03-10T15:13:22Z
dc.date.available2023-03-10T15:13:22Z
dc.date.issued2022-01-15
dc.identifier.citationMoon, H. J., Haroutunian, V., & Zhao, L. (2022). Human apolipoprotein E isoforms are differentially sialylated and the sialic acid moiety in ApoE2 attenuates ApoE2-Aβ interaction and Aβ fibrillation. Neurobiology of disease, 164, 105631. https://doi.org/10.1016/j.nbd.2022.105631en_US
dc.identifier.urihttps://hdl.handle.net/1808/34034
dc.description.abstractThe APOE genotype is the most prominent genetic risk factor for the development of late-onset Alzheimer’'s disease (LOAD); however, the underlying mechanisms remain unclear. In the present study, we found that the sialylation profiles of ApoE protein in the human brain are significantly different among the three isoforms, with ApoE2 exhibiting the most abundant sialic acid modification whereas ApoE4 had the least. We further observed that the sialic acid moiety in ApoE2 significantly affected the interaction between ApoE2 and Aβ peptides. The removal of sialic acid in ApoE2 increased the ApoE2 binding affinity for the Aβ17–24 region of Aβ and promoted Aβ fibrillation. These findings provide a plausible explanation for the well-documented differential roles of ApoE isoforms in Aβ pathogenesis. Specifically, compared to the other two isotypes, the higher expression of sialic acid in ApoE2 may contribute to the less potent interaction between ApoE2 and Aβ and ultimately the slower rate of brain Aβ deposition, a mechanism thought to underlie ApoE2-mediated decreased risk for AD. Future studies are warranted to determine whether the differential sialylation in ApoE isoforms may also contribute to some of their other distinct properties, such as their divergent preferences in associations with lipids and lipoproteins, as well as their potential impact on neuroinflammation through modulation of microglial Siglec activity. Overall, our findings lead to the insight that the sialic acid structure is an important posttranslational modification (PTM) that alters ApoE protein functions with relevance for AD.en_US
dc.publisherElsevieren_US
dc.rights© 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license.en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0en_US
dc.subjectLate-onset Alzheimer's disease (LOAD)en_US
dc.subjectApolipoprotein E (ApoE)en_US
dc.subjectAmyloid-β (Aβ)en_US
dc.subjectApoE-Aβ interactionen_US
dc.subjectSialic aciden_US
dc.subjectSialylationen_US
dc.titleHuman apolipoprotein E isoforms are differentially sialylated and the sialic acid moiety in ApoE2 attenuates ApoE2-Aβ interaction and Aβ fibrillationen_US
dc.typeArticleen_US
kusw.kuauthorMoon, Hee-Jung
kusw.kuauthorZhao, Liqin
kusw.kudepartmentPharmacology and Toxicologyen_US
kusw.kudepartmentNeuroscience Graduate Programen_US
dc.identifier.doi10.1016/j.nbd.2022.105631en_US
kusw.oaversionScholarly/refereed, publisher versionen_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.identifier.pmidPMC9809161en_US
dc.rights.accessrightsopenAccessen_US


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© 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license.
Except where otherwise noted, this item's license is described as: © 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license.