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Modelling APOE epsilon 3/4 allele-associated sporadic Alzheimer's disease in an induced neuron : Modelling APOE ϵ3/4 allele-associated sporadic Alzheimer's disease in an induced neuron
DC Field | Value | Language |
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dc.contributor.author | Kim, Hongwon | - |
dc.contributor.author | Yoo, Junsang | - |
dc.contributor.author | Shin, Jaein | - |
dc.contributor.author | Chang, Yujung | - |
dc.contributor.author | Jung, Junghyun | - |
dc.contributor.author | Jo, Dong-Gyu | - |
dc.contributor.author | Kim, Janghwan | - |
dc.contributor.author | Jang, Wonhee | - |
dc.contributor.author | Lengner, Christopher J. | - |
dc.contributor.author | Kim, Byung-Soo | - |
dc.contributor.author | Kim, Jongpil | - |
dc.date.accessioned | 2024-06-13T02:12:49Z | - |
dc.date.available | 2024-06-13T02:12:49Z | - |
dc.date.created | 2018-06-19 | - |
dc.date.issued | 2017-08 | - |
dc.identifier.citation | Brain, Vol.140 No.8, pp.2193-2209 | - |
dc.identifier.issn | 0006-8950 | - |
dc.identifier.uri | https://hdl.handle.net/10371/204261 | - |
dc.description.abstract | The recent generation of induced neurons by direct lineage conversion holds promise for in vitro modelling of sporadic Alzheimer's disease. Here, we report the generation of induced neuron-based model of sporadic Alzheimer's disease in mice and humans, and used this system to explore the pathogenic mechanisms resulting from the sporadic Alzheimer's disease risk factor apolipoprotein E (APOE) epsilon 3/4 allele. We show that mouse and human induced neurons overexpressing mutant amyloid precursor protein in the background of APOE epsilon 3/4 allele exhibit altered amyloid precursor protein (APP) processing, abnormally increased production of amyloid-beta(42) and hyperphosphorylation of tau. Importantly, we demonstrate that APOE epsilon 3/4 patient induced neuron culture models can faithfully recapitulate molecular signatures seen in APOE epsilon 3/4-associated sporadic Alzheimer's disease patients. Moreover, analysis of the gene network derived from APOE epsilon 3/4 patient induced neurons reveals a strong interaction between APOE epsilon 3/4 and another Alzheimer's disease risk factor, desmoglein 2 (DSG2). Knockdown of DSG2 in APOE epsilon 3/4 induced neurons effectively rescued defective APP processing, demonstrating the functional importance of this interaction. These data provide a direct connection between APOE epsilon 3/4 and another Alzheimer's disease susceptibility gene and demonstrate in proof of principle the utility of induced neuron-based modelling of Alzheimer's disease for therapeutic discovery. | - |
dc.language | 영어 | - |
dc.publisher | Oxford University Press | - |
dc.title | Modelling APOE epsilon 3/4 allele-associated sporadic Alzheimer's disease in an induced neuron | - |
dc.title.alternative | Modelling APOE ϵ3/4 allele-associated sporadic Alzheimer's disease in an induced neuron | - |
dc.type | Article | - |
dc.identifier.doi | 10.1093/brain/awx144 | - |
dc.citation.journaltitle | Brain | - |
dc.identifier.wosid | 000406345900026 | - |
dc.identifier.scopusid | 2-s2.0-85028299630 | - |
dc.citation.endpage | 2209 | - |
dc.citation.number | 8 | - |
dc.citation.startpage | 2193 | - |
dc.citation.volume | 140 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Kim, Byung-Soo | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | PLURIPOTENT STEM-CELLS | - |
dc.subject.keywordPlus | DIRECT LINEAGE CONVERSION | - |
dc.subject.keywordPlus | DOPAMINERGIC-NEURONS | - |
dc.subject.keywordPlus | HUMAN FIBROBLASTS | - |
dc.subject.keywordPlus | A-BETA | - |
dc.subject.keywordPlus | FUNCTIONAL-NEURONS | - |
dc.subject.keywordPlus | APOLIPOPROTEIN-E | - |
dc.subject.keywordPlus | INTERACTION NETWORKS | - |
dc.subject.keywordPlus | MOUSE FIBROBLASTS | - |
dc.subject.keywordPlus | TRANSGENIC MICE | - |
dc.subject.keywordAuthor | Alzheimer&apos | - |
dc.subject.keywordAuthor | s disease | - |
dc.subject.keywordAuthor | amyloid-beta | - |
dc.subject.keywordAuthor | neuroprotection | - |
dc.subject.keywordAuthor | APP | - |
dc.subject.keywordAuthor | APOE | - |
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