Genetic variants beyond amyloid and tau associated with cognitive decline

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dc.contributor.authorKim, Hang-Raiko
dc.contributor.authorLee, Taeyeopko
dc.contributor.authorChoi, Jung Kyoonko
dc.contributor.authorJeong, Yongko
dc.date.accessioned2020-12-10T08:10:23Z-
dc.date.available2020-12-10T08:10:23Z-
dc.date.created2020-11-30-
dc.date.issued2020-10-
dc.identifier.citationNEUROLOGY, v.95, no.17, pp.2366 - 2377-
dc.identifier.issn0028-3878-
dc.identifier.urihttp://hdl.handle.net/10203/278138-
dc.description.abstractObjective 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.languageEnglish-
dc.publisherLIPPINCOTT WILLIAMS WILKINS-
dc.titleGenetic variants beyond amyloid and tau associated with cognitive decline-
dc.typeArticle-
dc.identifier.wosid000587817900020-
dc.identifier.scopusid2-s2.0-85094932425-
dc.type.rimsART-
dc.citation.volume95-
dc.citation.issue17-
dc.citation.beginningpage2366-
dc.citation.endingpage2377-
dc.citation.publicationnameNEUROLOGY-
dc.identifier.doi10.1212/WNL.0000000000010724-
dc.contributor.localauthorChoi, Jung Kyoon-
dc.contributor.localauthorJeong, Yong-
dc.description.isOpenAccessY-
dc.type.journalArticleArticle-
dc.subject.keywordPlusBRAIN OXIDATIVE STRESS-
dc.subject.keywordPlusALZHEIMERS-DISEASE-
dc.subject.keywordPlusGLUTATHIONE DEPLETION-
dc.subject.keywordPlusFLUID-
dc.subject.keywordPlusPOPULATION-
dc.subject.keywordPlusEXPRESSION-
dc.subject.keywordPlusHYPOTHESIS-
dc.subject.keywordPlusREGIONS-
dc.subject.keywordPlusMARKERS-
dc.subject.keywordPlusMODEL-
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