Project description:Due to an increasingly aging population, the incidence of dementias such as Alzheimer’s disease are steadily rising, with recent estimates predicting >115million dementia sufferers by 2050. The ability to identify early markers in blood, which appear before the onset of clinical symptoms is of considerable interest to allow early intervention, particularly in “high risk” groups such as those with Type 2 Diabetes (T2D). Here we present longitudinal genome-wide DNA methylation data comparing 18 elderly individuals with T2D who developed pre-symptomatic dementia within an 18 month period following baseline assessment to 18 age, sex and education matched controls who maintained normal cognitive function. We identified a highly significant overlap in the effect size of the top-ranked methylation sites at baseline and follow-up, and identified 8 robust loci, some of which have been previously related to neurodegenerative processes, which were consistently differentially methylated prior to symptoms at baseline, and at 18 month follow up, when a diagnosis of pre-symptomatic dementia had been provided. Finally we show a significant overlap in the effect size of the top-ranked methylation sites in converters, only after they develop symptoms of pre-symptomatic dementia, with changes at the same loci in blood samples from patients with clinically-diagnosed Alzheimer’s disease.
Project description: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:Analysis of neutrophils purified from peripheral blood of patients with symptomatic and pre-symptomatic type 1 diabetes (T1D), at risk of T1D, and healthy controls.
Project description:Genome wide DNA methylation profiling of cord blood cells obtained from gestational diabetes mellitus (GDM) pregnancies. The Illumina EPIC methylation beadchip array was used to obtain DNA methylation profiles across approximately 850,000 CpG dinucleotide methylation loci in DNA isolated from cord blood. Samples include 165 GDM subjects.
Project description:The current study aimed to address the hypothesis that programmed expression of key miRNAs in skeletal muscle mediates the development of insulin resistance, and consequently long-term health. We thus examined microRNA signatures in skeletal muscle of unmedicated newly diagnosed human pre-diabetics and type 2 diabetics. Skeletal muscle biopsies were obtained from the vastus lateralis from males with pre-diabetes (PD, n=5) or type 2 diabetes mellitus (T2DM, n=6) along with age and sex-matched healthy volunteers (H, n=5). Ramaciotti Centre for Genomics (UNSW, sydney, Australia)
Project description:First version (1.0) of the Eindhoven Diabetes Simulator (EDES) model, describing postprandial glucose and insulin dynamics for a healthy human. Model can also be used to simulate insulin resistance (pre-diabetes, Metabolic Syndrome) and Type 2 Diabetes Mellitus (T2DM). Next to simulating a meal, the model can simulate oral glucose tolerance tests (OGTT's).
Project description:High blood glucose level is one of the main characteristics of diabetes mellitus (DM). It is speculated that longevity families may have certain advantages in blood glucose regulation. But till now, limited information on these items is reported. In this study, a TMT- based comparative quantitative proteomics analysis was used to reveal the changes of plasma proteomics profiles between longevity subjects and non-longevity area participants in order to identify plasma proteins associated with glucose metabolism in longevity population and to explore the characteristics of blood glucose regulation in longevity population
Project description:Systems approaches have been used to describe molecular signatures driving immunity to influenza vaccination in humans. Whether such signatures are similar across multiple seasons, and in diverse populations is unknown. We applied systems approaches to study immune responses in young and, elderly subjects vaccinated with the seasonal influenza vaccine across 5 consecutive seasons. During the 2010 Influenza season, healthy adults were vaccinated with TIV, and blood samples isolated at days 0, 3, 7 post-vaccination. Microarrays were performed using total RNA extracted from the peripheral blood mononuclear cells of vaccinees.
Project description:Systems approaches have been used to describe molecular signatures driving immunity to influenza vaccination in humans. Whether such signatures are similar across multiple seasons, and in diverse populations is unknown. We applied systems approaches to study immune responses in young and, elderly subjects vaccinated with the seasonal influenza vaccine across 5 consecutive seasons. During the 2011 Influenza season, healthy adults were vaccinated with TIV, and blood samples isolated at days 0, 3, 7 post-vaccination. Microarrays were performed using total RNA extracted from the peripheral blood mononuclear cells of vaccinees.
