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• W2897280539 abstract "Growing evidence showed that epigenetic alterations play a role in Alzheimer's Disease (AD). Findings suggest that AD patients have a relatively repressed chromatin state and reduced plasticity. Here we explore the epigenetic alteration in AD by comparing genome-wide DNA methylation profiles of the superior temporal gyrus (STG) region from postmortem brains between AD patients and cognitively normal controls. Samples from the STG region of postmortem brains from 91 AD patients and 60 controls were collected by Banner Sun Health Research Institute. Genomic DNA and total RNA were simultaneous purified from brain samples using AllPrep DNA/RNA/miRNA Universal Kit (QIAGEN©). Genomic DNA was subject to genome-wide methylation profiling using Illumina© Infinium MethylationEPIC BeadChip. After data quality checking and filtering, the methylation levels were normalized using Dasen method. We used SVA package to detect batch effect and included top 5 surrogate variables in addition to sex and age as covariates in the analysis using limma to identify differentially methylated positions (DMPs). We identified 577 DMPs between AD patients and cognitively normal control (FDR < 0.05). Several of them were close to genes with genome wide significant associations to AD, including CD2AP, ABCA7, CLU, SLC24A4, SQSTM1 and ACE. Of them, CLU and ABCA7 were known to exhibit epigenetic alterations in AD patients. Other known AD associated differentially methylated genes such as TBXA2R, PCNT also contained DMPs in our result. Weighted gene set enrichment analysis of the DMPs showed that genes in canonical pathways such as E-cadherin signaling, ACE2 pathway, PTEN pathway, and IGF-1/mTOR pathway were significantly enriched (FDR <0.1). Current data support previous observations that AD patients have a distinct DNA methylation profile compared with cognitively normal controls. We validated several known differentially methylated genes associated with AD and discovered new differentially methylated epigenetic markers. The enrichment of differentially methylated genes in signaling pathways critical in oxidative stress, neuroinflammation, aging and cognitive decline indicates that DNA methylation may have profound effect in the progression of AD. Further studies are needed to validate our findings." @default.
• W2897280539 created "2018-10-26" @default.
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• W2897280539 date "2018-07-01" @default.
• W2897280539 modified "2023-10-16" @default.
• W2897280539 title "P4‐241: EPIGENETIC MARKERS IN THE SUPERIOR TEMPORAL GYRUS OF POSTMORTEM BRAINS FROM ALZHEIMER'S DISEASE PATIENTS" @default.
• W2897280539 doi "https://doi.org/10.1016/j.jalz.2018.07.062" @default.
• W2897280539 hasPublicationYear "2018" @default.
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