Methylation arrays (MethylationEPIC) of peripheral blood of individuals with evolving dementia
Ontology highlight
ABSTRACT: DNA methylation changes have been associated to dementia and cognitive decline. However, it is not clear if these changes arise before or during the onset of the pathologies. Here, using Illumina's MethylationEPIC array technology, we have profiled the methylomes of elderly, cognitively healthy individuals which go on to develop dementia or stay cognitively healthy. The subjects are profiled at a pre-diagnosis stage and at 4 year follow-up post-diagnosis.
Project description:Epidemiological studies have associated maternal metabolic conditions such as obesity and gestational diabetes with poor health outcomes in the offspring. Epigenetic mechanisms may help explain the intrauterine influence that mothers have on their offspring during pregnancy. Here, using Illumina's MethylationEPIC array technology, we have longitudinally profiled the blood methylomes of children born to mothers with obesity and obesity with gestational diabetes, and healthy controls, during the first year of life (measurements at 0, cord blood; 6 and 12 months, peripheral blood).
Project description:Type 1 diabetes (1a) diabetes is an autoimmune disease in which both environmental and genetic factors play a role. Epigenetic marks such as DNA methylation, being molecular links between the environment and the genome function, are sound candidates for the explanation of part of the aetiology and mechanisms of the disease. Here, the methylomes of the whole blood of 18 adult individuals with T1D were profiled using Illumina's MethylationEPIC array technology.
Project description:Epigenetic remodeling is central to understanding the molecular mechanisms that occur and drive human aging. In fact, DNA methylation clocks are capable of estimating biological age, which determines human lifespan and healthspan. Here, using Illumina's MethylationEPIC array technology, we have profiled the DNA methylation landscape of peripheral whole blood samples from adult individuals ranging in age from 19 to 96 years.
Project description:Extensive epigenetic remodelling takes place during early life; however, the alterations of DNA methylation that occur during this period have not been sufficiently addressed by longitudinal studies. We made use of the most recent Illumina MethylationEPIC Beadchip platform to characterize genome-wide DNA methylation changes observed through the first 10 years of life in longitudinal blood samples of 11 subjects. We described numerous changes during the first 5 years, while many less alterations in the following 5 year period. Interestingly, we identified a subset of persistent DNA methylation changes of considerable magnitude along the first 10 years of life. Moreover, our data demonstrated that genes that suffer simultaneous hyper- and hypomethylation are functionally different from genes that are exclusively hyper- or hypomethylated. Furthermore, our results evidence that enhancer-associated methylation changes are different for the gain or loss of methylation. throughout hematopoietic maturation by analyzing multiple hematopoietic cell types at different developmental stages. We identified a plethora of DNA methylation changes that occur during human hematopoietic differentiation. Interestingly, we observed that T lymphocytes display a substantial enhancement of de novo CpG hypermethylation as compared to other hematopoietic cell populations.
Project description:Dengue virus is the most common arbovirus worldwide and represents a significant public health concern. To date, chronic Dengue infections have not been previously reported. While investigating the etiology of central nervous system (CNS) disease in a patient presenting with progressive dementia, we elucidated a chronic dengue infection within the CNS. Comprehensive viral immune responses in both serum and cerebrospinal fluid (CSF) were profiled by a phage-display assay (VirScan). Enrichment of Dengue viral antibodies were detected in the CSF as compared to the serum. No virus was detected in serum or CSF, but post-mortem analysis confirmed Dengue virus in the brain by quantitative polymerase chain reaction (PCR), immunohistochemistry, RNAscope and sequencing. Dengue virus was detectable by PCR and sequencing from brain biopsy tissue collected 33 months ante-mortem, confirming a chronic infection. Comprehensive antibody profiling assays can aid in the diagnosis of encephalitis of unknown etiologies. Our findings suggest that Dengue virus infections may persist in the CNS and should be considered in patients with progressive dementia in endemic regions or with relevant travel history.
Project description:Nanomaterials have lots of promising applications, and concern has risen about their impact to human health. Here, we have analyzed the genome-wide DNA methylation changes associated to the exposure to reduced graphene oxide (rGO) in human lung epithelial cells. Six conditions were assayed, with two technical replicates per condition (12 arrays in total): control, 1 and 10 µg/mL of rGO for 15 or 30 days of exposure.
Project description:Dementia with Lewy bodies (DLB) is a common form of dementia with known genetic and environmental interactions. However, the underlying epigenetic mechanisms which reflect these gene-environment interactions are poorly studied. Herein, we measured genome-wide DNA methylation profiles of post-mortem brain tissue (Broadmann area 7) from 15 pathologically confirmed DLB brains and compared them with 16 cognitively normal controls using Illumina MethylationEPIC arrays. We identified 17 significantly differentially methylated CpGs (DMCs) and 17 differentially methylated regions (DMRs) between the groups. The DMCs are mainly located at the CpG islands, promoter and first exon regions. Genes associated with the DMCs are linked to “Parkinson disease” and “metabolic pathway”, as well as the diseases of “severe intellectual disability” and “mood disorders”. Overall, our study highlights previously unreported DMCs offering insights into DLB pathogenesis with the possibility that some of these could be used as biomarkers of DLB in the future.
Project description:There are many subtypes of dementia without any minimally invasive, low-cost and efficient diagnostic biomarkers. MicroRNA (miRNA) are easily gained and accessible from patients, which may be a promising biomarker for dementia diagnosis and differential diagnosis. We make a completely expression analysis of serum miRNA from 24 participants including post-stroke cognitive impairment (PSCI) group (n=6), post-stroke non-cognitive impairment (PSCI) group, Alzheimer's Disease (AD) group (n=6) and normal control group (NC) group (n=6). Different expression miRNA (DE -miRNA) were screened by LIMMA ebayes method, Benjamini-Hochberg check and fold change (P < 0.05, |log2FC|≥1), we construct a DE-miRNA-key gene-signaling pathway network, the roles of DE-miRNA and related genes and signaling pathways in AD and PSCI were deduced through comprehensive network construction and literature search.
Project description:With the aging population, there is a growing focus on dementia, especially Alzheimer’s disease (AD). The molecular basis underlying the pathogenesis of AD is gradually being elucidated. Increasing evidence has shown that the immunological function of leukocytes plays a crucial role in the development of neurodegenerative disorders. However, there have been few studies among the Taiwanese population. The aim of this study was to investigate potential biomarkers for early diagnosis of Alzheimer’s disease from blood leukocytes. Experiment Overall Design: The peripheral blood mononuclear cells (PBMC) transcriptomes from 5 patients with mild cognitive impairment (MCI), 4 AD, as well as 4 normal controls (NC), were analyzed by microarray analysis.
Project description:With the aging population, there is a growing focus on dementia, especially Alzheimer’s disease (AD). The molecular basis underlying the pathogenesis of AD is gradually being elucidated. Increasing evidence has shown that the immunological function of leukocytes plays a crucial role in the development of neurodegenerative disorders. However, there have been few studies among the Taiwanese population. The aim of this study was to investigate potential biomarkers for early diagnosis of Alzheimer’s disease from blood leukocytes.