Project description:Epigenome Analysis of Post-Mortem Human Temporal Pole Brain Tissue For more information, please refer to DOI: 10.3233/JAD-141989 Temporal Pole regions from 24 age-matched causcasian males: 8 samples which died of normal causes, 8 samples with Alzheimer's disease (stage 3/4) and 8 samples with dementia with lewy bodies
Project description:Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that is characterized by progressive neuropathology and cognitive decline. We performed a cross-tissue analysis of methylomic variation in AD using samples from three independent human post-mortem brain cohorts. We identified a differentially methylated region in the ankyrin 1 (ANK1) gene that was associated with neuropathology in the entorhinal cortex, a primary site of AD manifestation. This region was confirmed as being substantially hypermethylated in two other cortical regions (superior temporal gyrus and prefrontal cortex), but not in the cerebellum, a region largely protected from neurodegeneration in AD, or whole blood obtained pre-mortem from the same individuals. Neuropathology-associated ANK1 hypermethylation was subsequently confirmed in cortical samples from three independent brain cohorts. This study represents, to the best of our knowledge, the first epigenome-wide association study of AD employing a sequential replication design across multiple tissues and highlights the power of this approach for identifying methylomic variation associated with complex disease. For the first (discovery) stage of our analysis, we used multiple tissues from donors (N = 122) archived in the MRC London Brainbank for Neurodegenerative Disease. From each donor, we isolated genomic DNA from four brain regions (EC, superior temporal gyrus (STG), prefrontal cortex (PFC) and CER) and, where available, from whole blood obtained pre-mortem. Our analyses focused on identifying differentially methylated positions (DMPs) associated with Braak staging, a standardized measure of neurofibrillary tangle burden determined at autopsy.
Project description:Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that is characterized by progressive neuropathology and cognitive decline. We performed a cross-tissue analysis of methylomic variation in AD using samples from three independent human post-mortem brain cohorts. We identified a differentially methylated region in the ankyrin 1 (ANK1) gene that was associated with neuropathology in the entorhinal cortex, a primary site of AD manifestation. This region was confirmed as being substantially hypermethylated in two other cortical regions (superior temporal gyrus and prefrontal cortex), but not in the cerebellum, a region largely protected from neurodegeneration in AD, or whole blood obtained pre-mortem from the same individuals. Neuropathology-associated ANK1 hypermethylation was subsequently confirmed in cortical samples from three independent brain cohorts. This study represents, to the best of our knowledge, the first epigenome-wide association study of AD employing a sequential replication design across multiple tissues and highlights the power of this approach for identifying methylomic variation associated with complex disease.
Project description:We set up a pilot study using Affymetrix Gene Chip® Porcine Genome Arrays to evaluate the impact of time lags from death on gene expression profiling of porcine skeletal muscle at four post mortem time points (up to 24 hrs) during the routine processing of fresh tights Post mortem skeletal muscle samples were obtained from three commercial hybrid pigs of female sex (of about 160 kg each) raised in the same commercial farm and slaughtered under normal conditions at the same abattoir within 1 minute of each other after stunning by CO2 (concentration 87%) using a dip lift system (Butina, Denmark). A portion of semimembranosus muscle (3-5 g) was sampled from the left legs at 20 minutes (T0) after death following the normal operation of the abattoir. Other samples were collected from the same muscle at the same position after 2 (T1), 6 (T2) and 24 (T3) hrs post mortem in the same abattoir following the cold chain at the abattoir until 4 °C. After sampling, tissues were snap frozen in liquid nitrogen and stored at -80 °C till RNA extraction.