Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep34051
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dc.titleRescue of Early bace-1 and Global DNA Demethylation by S-Adenosylmethionine Reduces Amyloid Pathology and Improves Cognition in an Alzheimer's Model
dc.contributor.authorDo Carmo, S
dc.contributor.authorHanzel, C.E
dc.contributor.authorJacobs, M.L
dc.contributor.authorMacHnes, Z
dc.contributor.authorIulita, M.F
dc.contributor.authorYang, J
dc.contributor.authorYu, L
dc.contributor.authorDucatenzeiler, A
dc.contributor.authorDanik, M
dc.contributor.authorBreuillaud, L.S
dc.contributor.authorBennett, D.A
dc.contributor.authorSzyf, M
dc.contributor.authorCuello, A.C
dc.date.accessioned2020-10-22T02:48:38Z
dc.date.available2020-10-22T02:48:38Z
dc.date.issued2016
dc.identifier.citationDo Carmo, S, Hanzel, C.E, Jacobs, M.L, MacHnes, Z, Iulita, M.F, Yang, J, Yu, L, Ducatenzeiler, A, Danik, M, Breuillaud, L.S, Bennett, D.A, Szyf, M, Cuello, A.C (2016). Rescue of Early bace-1 and Global DNA Demethylation by S-Adenosylmethionine Reduces Amyloid Pathology and Improves Cognition in an Alzheimer's Model. Scientific Reports 6 : 34051. ScholarBank@NUS Repository. https://doi.org/10.1038/srep34051
dc.identifier.issn20452322
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/178859
dc.description.abstractGeneral DNA hypomethylation is associated with Alzheimer's disease (AD), but it is unclear when DNA hypomethylation starts or plays a role in AD pathology or whether DNA re-methylation would rescue early amyloid-related cognitive impairments. In an APP transgenic mouse model of AD-like amyloid pathology we found that early intraneuronal amyloid beta build-up is sufficient to unleash a global and beta-site amyloid precursor protein cleaving enzyme 1 (bace-1) DNA demethylation in AD-vulnerable brain regions. S-adenosylmethionine administration at these early stages abolished this hypomethylation, diminished the amyloid pathology and restored cognitive capabilities. To assess a possible human significance of findings, we examined the methylation at 12 CpGs sites in the bace-1 promoter, using genome-wide DNA methylation data from 740 postmortem human brains. Thus, we found significant associations of bace-1 promoter methylation with ?-amyloid load among persons with AD dementia, and PHFtau tangle density. Our results support a plausible causal role for the earliest amyloid beta accumulation to provoke DNA hypomethylation, influencing AD pathological outcomes. © 2016 The Author(s).
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20201031
dc.typeArticle
dc.contributor.departmentPHARMACOLOGY
dc.description.doi10.1038/srep34051
dc.description.sourcetitleScientific Reports
dc.description.volume6
dc.description.page34051
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