Chen K.-L.Wang S.S.-S.Yang Y.-Y.Yuan R.-Y.Chen R.-M.Hu C.-J.2019-05-092019-05-0920090006291Xhttps://scholars.lib.ntu.edu.tw/handle/123456789/406755Amyloid-£] (A£]) is the core component of senile plaques, which are the pathological markers for Alzheimer's disease and cerebral amyloid angiopathy. DNA methylation/demethylation plays a crucial role in gene regulation and could also be responsible for presentation of senescence. Oxidative stress, which may be induced by A£], is thought to be an important contributor of DNA hyper-methylation; however, contradicting this is the fact that global DNA hypo-methylation has been found in aging brains. It therefore remains largely unknown as to whether A£] does in fact cause DNA methylation/demethylation. Neprilysin (NEP) is one of the enzymes responsible for A£] degradation, with its expression decreasing in both Alzheimer and aging brains. Using high-performance liquid chromatography (HPLC), we explore whether A£] is responsible for alteration of the global DNA methylation status on a murine cerebral endothelial cells model, and also use methylation-specific PCR (MSPCR) to examine whether DNA methylation status is altered on the NEP promoter region. We find that A£] reduces global DNA methylation whilst increasing NEP DNA methylation and further suppressing the NEP expression in mRNA and protein levels. Our results support that A£] induces epigenetic effects, implying that DNA methylation may be part of a vicious cycle involving the reduction in NEP expression along with a resultant increase in A£] accumulation, and that A£] may induce global DNA hypo-methylation. ? 2008 Elsevier Inc. All rights reserved.Alzheimer's diseaseAmyloid-£]Cerebral amyloid angiopathyDNA methylationNeprilysinjournal article10.1016/j.bbrc.2008.10.1732-s2.0-56949102195https://www.scopus.com/inward/record.uri?eid=2-s2.0-56949102195&doi=10.1016%2fj.bbrc.2008.10.173&partnerID=40&md5=ef160eba73c3ab045555589ff25ced48