Deficiency in LRP6-Mediated Wnt Signaling Contributes to Synaptic Abnormalities and Amyloid Pathology in Alzheimer's Disease
DC Field | Value | Language |
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dc.contributor.author | Liu, Chia-Chen | - |
dc.contributor.author | Tsai, Chih-Wei | - |
dc.contributor.author | Deak, Ferenc | - |
dc.contributor.author | Rogers, Justin | - |
dc.contributor.author | Penuliar, Michael | - |
dc.contributor.author | Sung, You Me | - |
dc.contributor.author | Maher, James N. | - |
dc.contributor.author | Fu, Yuan | - |
dc.contributor.author | Li, Xia | - |
dc.contributor.author | Xu, Huaxi | - |
dc.contributor.author | Estus, Steven | - |
dc.contributor.author | Hoe, Hyang-Sook | - |
dc.contributor.author | Fryer, John D. | - |
dc.contributor.author | Kanekiyo, Takahisa | - |
dc.contributor.author | Bu, Guojun | - |
dc.date.accessioned | 2023-08-16T09:51:38Z | - |
dc.date.available | 2023-08-16T09:51:38Z | - |
dc.date.created | 2022-01-11 | - |
dc.date.issued | 2014-10 | - |
dc.identifier.issn | 0896-6273 | - |
dc.identifier.uri | http://scholarworks.bwise.kr/kbri/handle/2023.sw.kbri/887 | - |
dc.description.abstract | Alzheimer's disease (AD) is an age-related neurological disorder characterized by synaptic loss and dementia. The low-density lipoprotein receptor-related protein 6 (LRP6) is an essential coreceptor for Wnt signaling, and its genetic variants have been linked to AD risk. Here we report that neuronal LRP6-mediated Wnt signaling is critical for synaptic function and cognition. Conditional deletion of Lrp6 gene in mouse forebrain neurons leads to age-dependent deficits in synaptic integrity and memory. Neuronal LRP6 deficiency in an amyloid mouse model also leads to exacerbated amyloid pathology due to increased APP processing to amyloid-beta. In humans, LRP6 and Wnt signaling are significantly downregulated in AD brains, likely by a mechanism that depends on amyloid-b. Our results define a critical pathway in which decreased LRP6-mediated Wnt signaling, synaptic dysfunction, and elevated Ab synergistically accelerate AD progression and suggest that restoring LRP6-mediated Wnt signaling can be explored as a viable strategy for AD therapy. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | CELL PRESS | - |
dc.title | Deficiency in LRP6-Mediated Wnt Signaling Contributes to Synaptic Abnormalities and Amyloid Pathology in Alzheimer's Disease | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Hoe, Hyang-Sook | - |
dc.identifier.doi | 10.1016/j.neuron.2014.08.048 | - |
dc.identifier.scopusid | 2-s2.0-84907985969 | - |
dc.identifier.wosid | 000342502800011 | - |
dc.identifier.bibliographicCitation | NEURON, v.84, no.1, pp.63 - 77 | - |
dc.relation.isPartOf | NEURON | - |
dc.citation.title | NEURON | - |
dc.citation.volume | 84 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 63 | - |
dc.citation.endPage | 77 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Neurosciences & Neurology | - |
dc.relation.journalWebOfScienceCategory | Neurosciences | - |
dc.subject.keywordPlus | COMMON GENETIC-VARIATION | - |
dc.subject.keywordPlus | BETA-CATENIN | - |
dc.subject.keywordPlus | LRP6 | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | LOW-DENSITY-LIPOPROTEIN-RECEPTOR-RELATED-PROTEIN-6 | - |
dc.subject.keywordPlus | DEGENERATION | - |
dc.subject.keywordPlus | TRANSMISSION | - |
dc.subject.keywordPlus | DYSFUNCTION | - |
dc.subject.keywordPlus | GENERATION | - |
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