Please use this identifier to cite or link to this item:
http://hdl.handle.net/10397/95515
DC Field | Value | Language |
---|---|---|
dc.contributor | Department of Health Technology and Informatics | en_US |
dc.creator | Cheng, GWY | en_US |
dc.creator | Mok, KKS | en_US |
dc.creator | Yeung, SHS | en_US |
dc.creator | Kofler, J | en_US |
dc.creator | Herrup, K | en_US |
dc.creator | Tse, KH | en_US |
dc.date.accessioned | 2022-09-21T01:39:11Z | - |
dc.date.available | 2022-09-21T01:39:11Z | - |
dc.identifier.issn | 0022-3069 | en_US |
dc.identifier.uri | http://hdl.handle.net/10397/95515 | - |
dc.language.iso | en | en_US |
dc.publisher | Oxford University Press | en_US |
dc.rights | © The Author(s) 2022. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. | en_US |
dc.rights | This is a pre-copyedited, author-produced PDF of an article accepted for publication in Journal of Neuropathology & Experimental Neurology following peer review. The version of record Gerald Wai-Yeung Cheng, Kingston King-Shi Mok, Sunny Hoi-Sang Yeung, Julia Kofler, Karl Herrup, Kai-Hei Tse, Apolipoprotein E ε4 Mediates Myelin Breakdown by Targeting Oligodendrocytes in Sporadic Alzheimer Disease, Journal of Neuropathology & Experimental Neurology, Volume 81, Issue 9, September 2022, Pages 717–730 is available online at: https://doi.org/10.1093/jnen/nlac054. | en_US |
dc.subject | Alzheimer disease | en_US |
dc.subject | Amyloid-independent | en_US |
dc.subject | APOE4 | en_US |
dc.subject | Lipid transport | en_US |
dc.subject | Myelin | en_US |
dc.subject | Oligodendrocyte | en_US |
dc.title | Apolipoprotein E ε4 mediates myelin breakdown by targeting oligodendrocytes in sporadic Alzheimer disease | en_US |
dc.type | Journal/Magazine Article | en_US |
dc.identifier.spage | 717 | en_US |
dc.identifier.epage | 730 | en_US |
dc.identifier.volume | 81 | en_US |
dc.identifier.issue | 9 | en_US |
dc.identifier.doi | 10.1093/jnen/nlac054 | en_US |
dcterms.abstract | White matter degradation in the frontal lobe is one of the earliest detectable changes in aging and Alzheimer disease. The ε4 allele of apolipoprotein E (APOE4) is strongly associated with such myelin pathology but the underlying cellular mechanisms remain obscure. We hypothesized that, as a lipid transporter, APOE4 directly triggers pathology in the cholesterol-rich myelin sheath independent of AD pathology. To test this, we performed immunohistochemistry on brain tissues from healthy controls, sporadic, and familial Alzheimer disease subjects. While myelin basic protein expression was largely unchanged, in frontal cortex the number of oligodendrocytes (OLs) was significantly reduced in APOE4 brains independent of their Braak stage or NIA-RI criteria. This high vulnerability of OLs was confirmed in humanized APOE3 or APOE4 transgenic mice. A gradual decline of OL numbers was found in the aging brain without associated neuronal loss. Importantly, the application of lipidated human APOE4, but not APOE3, proteins significantly reduced the formation of myelinating OL in primary cell culture derived from Apoe-knockout mice, especially in cholesterol-depleted conditions. Our findings suggest that the disruption of myelination in APOE4 carriers may represent a direct OL pathology, rather than an indirect consequence of amyloid plaque formation or neuronal loss. | en_US |
dcterms.accessRights | open access | en_US |
dcterms.bibliographicCitation | Journal of neuropathology and experimental neurology, Sept. 2022, v. 81, no. 9, p. 717-730 | en_US |
dcterms.isPartOf | Journal of neuropathology and experimental neurology | en_US |
dcterms.issued | 2022-09 | - |
dc.identifier.eissn | 1554-6578 | en_US |
dc.description.validate | 202209 bckw | en_US |
dc.description.oa | Accepted Manuscript | en_US |
dc.identifier.FolderNumber | RGC-B2-0612, a2221 | - |
dc.identifier.SubFormID | 47095 | - |
dc.description.fundingSource | RGC | en_US |
dc.description.fundingSource | Others | en_US |
dc.description.fundingText | National Institute of Health | en_US |
dc.description.pubStatus | Published | en_US |
dc.description.oaCategory | Green (AAM) | en_US |
Appears in Collections: | Journal/Magazine Article |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Cheng_Apolipoprotein_E_Ε4.pdf | Pre-Published version | 8.95 MB | Adobe PDF | View/Open |
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