DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Hang-Rai | ko |
dc.contributor.author | Lee, Taeyeop | ko |
dc.contributor.author | Choi, Jung Kyoon | ko |
dc.contributor.author | Jeong, Yong | ko |
dc.date.accessioned | 2020-12-10T08:10:23Z | - |
dc.date.available | 2020-12-10T08:10:23Z | - |
dc.date.created | 2020-11-30 | - |
dc.date.issued | 2020-10 | - |
dc.identifier.citation | NEUROLOGY, v.95, no.17, pp.2366 - 2377 | - |
dc.identifier.issn | 0028-3878 | - |
dc.identifier.uri | http://hdl.handle.net/10203/278138 | - |
dc.description.abstract | Objective To identify single nucleotide polymorphisms (SNPs) associated with cognitive decline independent of beta-amyloid (A beta) and tau pathology in Alzheimer disease (AD). Methods Discovery and replication datasets consisting of 414 individuals (94 cognitively normal control [CN], 185 with mild cognitive impairment [MCI], and 135 with AD) and 72 individuals (22 CN, 39 with MCI, and 11 with AD), respectively, were obtained from the Alzheimer's Disease Neuroimaging Initiative database. Genome-wide association analysis was conducted to identify SNPs associated with individual cognitive function (measured with the Mini-Mental State Examination and Alzheimer's Disease Assessment Scale-Cognitive Subscale) while controlling for the level of A beta and tau (measured as CSF phosphorylated-tau/A beta(1-42)). Gene ontology analysis was performed on SNP-associated genes. Results We identified 1 significant (rs55906536, beta = -1.91, standard error 0.34, p = 4.07 x 10(-8)) and 4 suggestive variants on chromosome 6 that were associated with poorer cognitive function. Congruent results were found in the replication data. A structural equation model showed that the identified SNP deteriorated cognitive function partially through cortical thinning of the brain in a region-specific manner. Furthermore, a bioinformatics analysis showed that the identified SNPs were associated with genes related to glutathione metabolism. Conclusions In this study, we identified SNPs related to cognitive decline in a manner that could not be explained by A beta and tau levels. Our findings provide insight into the complexity of AD pathogenesis and support the growing literature on the role of glutathione in AD. | - |
dc.language | English | - |
dc.publisher | LIPPINCOTT WILLIAMS WILKINS | - |
dc.title | Genetic variants beyond amyloid and tau associated with cognitive decline | - |
dc.type | Article | - |
dc.identifier.wosid | 000587817900020 | - |
dc.identifier.scopusid | 2-s2.0-85094932425 | - |
dc.type.rims | ART | - |
dc.citation.volume | 95 | - |
dc.citation.issue | 17 | - |
dc.citation.beginningpage | 2366 | - |
dc.citation.endingpage | 2377 | - |
dc.citation.publicationname | NEUROLOGY | - |
dc.identifier.doi | 10.1212/WNL.0000000000010724 | - |
dc.contributor.localauthor | Choi, Jung Kyoon | - |
dc.contributor.localauthor | Jeong, Yong | - |
dc.description.isOpenAccess | Y | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | BRAIN OXIDATIVE STRESS | - |
dc.subject.keywordPlus | ALZHEIMERS-DISEASE | - |
dc.subject.keywordPlus | GLUTATHIONE DEPLETION | - |
dc.subject.keywordPlus | FLUID | - |
dc.subject.keywordPlus | POPULATION | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | HYPOTHESIS | - |
dc.subject.keywordPlus | REGIONS | - |
dc.subject.keywordPlus | MARKERS | - |
dc.subject.keywordPlus | MODEL | - |
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