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:Cap analysis of gene expression (CAGE) and massive parallel sequencing were used to profile the promoterome of aged human brains from five regions, namely: caudate, frontal cortex, hippocampus, putamen and temporal cortex. 25 RNA libraries from post-mortem brain tissue (five caudate, five frontal, 5 hippocampus, 5 putamen, five temporal RNA libraries from seven individuals) were processed using CAGE protocol and CAGE tags derived from the 25 libraries were sequenced with Illumina.
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:Human post-mortem brain samples (middle temporal gyrus) from Alzheimer's disease (AD) and control individuals were processed for simultaneous coding and non-coding RNA-Seq analysis using a novel RNA-Seq protocol. These data were then analyzed for differential expression.
Project description:Vascular cell types are under-represented in standard single-nucleus RNA-Seq studies of human frozen post-mortem brain tissue. Using a novel microvessel-enrichment procedure allows to obtain highly purified fractions of vascular cell types and their corresponding parenchymal fraction of the same post-mortem brain tissue sample.