Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep34051
Title: Rescue of Early bace-1 and Global DNA Demethylation by S-Adenosylmethionine Reduces Amyloid Pathology and Improves Cognition in an Alzheimer's Model
Authors: Do 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 
Issue Date: 2016
Citation: Do 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
Rights: Attribution 4.0 International
Abstract: General 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).
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/178859
ISSN: 20452322
DOI: 10.1038/srep34051
Rights: Attribution 4.0 International
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