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Cortical hypermethylation across an extended region spanning the HOXA gene cluster on chromosome 7 is robustly associated with Alzheimer's disease neuropathology

ABSTRACT: Alzheimer's disease is a progressive neurodegenerative disorder that is hypothesized to involve epigenetic dysfunction. We undertook an epigenome-wide association study across three independent brain tissue cohorts (total n = 999) to identify differential DNA methylation associated with neuropathology in the superior temporal gyrus and prefrontal cortex. We present robust evidence for elevated DNA methylation associated with AD neuropathology across an extended region spanning the HOXA gene cluster on chromosome 7. Prefrontal cortex and superior temporal gyrus tissue from 147 individuals with varying levels of AD pathology. DNA modifications for these samples were quantified using the Illumina Infinium Human 450K Methylation Array.

ORGANISM(S): Homo sapiens

SUBMITTER: Rebecca Smith

PROVIDER: E-GEOD-80970 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Cortical hypermethylation across an extended region spanning the HOXA gene cluster on chromosome 7 is robustly associated with Alzheimer's disease neuropathology

Project description:Alzheimer's disease is a progressive neurodegenerative disorder that is hypothesized to involve epigenetic dysfunction. We undertook an epigenome-wide association study across three independent brain tissue cohorts (total n = 999) to identify differential DNA methylation associated with neuropathology in the superior temporal gyrus and prefrontal cortex. We present robust evidence for elevated DNA methylation associated with AD neuropathology across an extended region spanning the HOXA gene cluster on chromosome 7.

2016-08-01 | GSE80970 | GEO

Cross-tissue methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer’s disease neuropathology

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.

2014-08-17 | E-GEOD-59685 | biostudies-arrayexpress

Cross-tissue methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer’s disease neuropathology

2014-08-17 | GSE59685 | GEO

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Project description:Recent work has identified roles for environmental, genetic and epigenetic factors in AD risk. Motivated by suspected roles for epigenetic modifications in AD, we performed a genome-wide screen of DNA methylation using the Illumina Infinium HumanMethylation450 array platform on bulk tissue samples from the superior temporal gyrus (STG) of AD cases and non-demented controls. We paired a sliding window approach with linear models that account for age, gender, ethnicity, and estimated cellular proportions (neuronal vs. glial), to characterize AD-associated differentially methylated regions (DMRs). Whole DNA was extracted from STG tissue dissections collected from deceased individuals with and without Alzheimers Disease. DNA was bisulfite converted and global DNA methylation levels were assessed using Illumina Infinium HumanMethylation450 BeadChip.

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Epigenome wide association study of post-mortem Alzheimer’s Disease samples

Project description:Samples from 72 AD patients and 62 age-matched cognitively normal controls were assayed using Illumina© Infinium MethylationEPIC BeadChip. We performed an epigenome-wide association study (EWAS) to evaluate the epigenetic differences using post-mortem superior temporal gyrus (STG) and inferior frontal gyrus (IFG) samples. We performed an epigenome-wide association study (EWAS) to evaluate the epigenetic differences using post-mortem superior temporal gyrus (STG) and inferior frontal gyrus (IFG) samples.

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Non-demented individuals with intermediate Alzheimer's neuropathologies - neuronal expression (6 regions)

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2010-06-24 | E-GEOD-17757 | biostudies-arrayexpress

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Project description:The main goal of the study was to measure the epigenetic age (also known as DNA methylation age) of human tissues and to relate it to chronological age. Toward this end, we used the epigenetic clock software described in Horvath S (n=2013) DNA methylation age of human tissues and cell types. Genome Biology.2013, 14:R115. DOI: 10.1186/10.1186/gb-2013-14-10-r115 PMID: 24138928 Human DNA methylation Beadchip v1.2 was used to obtain n=260 Illumina DNA methylation array from the following human Brain regions: caudate nucleus (n=n=12), cingulate gyrus (n=n12), cerebellum (n=32), frontal cortex (n=41), hippocampus (n=25), midBrain (n=18), motor cortex (n=33), occipital cortex (n=33), parietal lobe (n=23), sensory cortex (n=12), temporal cortex (n=29), visual cortex (n=11).

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Genome-wide DNA methylation profiling in the superior temporal gyrus reveals epigenetic signatures associated with Alzheimer's disease

2015-12-18 | GSE76105 | GEO

Transcription profiling of human neurons from different brain regions derived from individuals with mild cognitive impairment

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