Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE59685 | GEO | 2014/08/17

SECONDARY ACCESSION(S): PRJNA256002

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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

Genome-wide H3K27ac profiles in post-mortem entorhinal cortex samples from Alzheimer's disease cases and controls

Project description:We quantified genome-wide levels of H3K27ac in post-mortem entorhinal cortex tissue samples, identifying widespread Alzheimer's disease (AD)-associated acetylomic variation. Differentially acetylated peaks were identified in the vicinity genes implicated in both tau and amyloid neuropathology (MAPT, APP, PSEN1, PSEN2), as well as genomic regions containing variants associated with sporadic late-onset AD (CR1, TOMM40). Both MAPT and PSEN2 are characterized by an extended hyperacetylated region upstream of the TSS mapping to enhancers in the brain. We show that genes annotated to AD-associated hyper- and hypoacetylated peaks are enriched for brain- and neuropathology-related functions.

2018-08-11 | GSE102538 | GEO

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. 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.

2016-08-01 | E-GEOD-80970 | biostudies-arrayexpress

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

2016-08-01 | GSE80970 | GEO

Methylomic profiling of human brain tissue supports a neurodevelopmental origin for schizophrenia.

Project description:Background: Schizophrenia is a severe neuropsychiatric disorder that is hypothesized to result from disturbances in early brain development, and there is mounting evidence to support a role for developmentally-regulated epigenetic variation in the molecular etiology of the disorder. Here, we describe a systematic study of schizophrenia-associated methylomic variation in the adult brain and its relationship to changes in DNA methylation across human fetal brain development. Results: We profile methylomic variation in matched prefrontal cortex and cerebellum brain tissue from schizophrenia patients and controls, identifying disease-associated differential DNA methylation at multiple loci, particularly in the prefrontal cortex, and confirming these differences in an independent set of adult brain samples. Our data reveal discrete modules of co-methylated loci associated with schizophrenia that are enriched for genes involved in neurodevelopmental processes and include loci implicated by genetic studies of the disorder. Methylomic data from human fetal cortex samples, spanning 23 to 184 days post-conception, indicates that disease-associated differentially methylated positions are significantly enriched for loci at which DNA methylation is dynamically altered during human fetal brain development. Conclusions: Our data support the hypothesis that schizophrenia has an important early neurodevelopmental component, and suggest that epigenetic mechanisms may mediate these effects. 33 post-mortem brain (prefrontal cortex) samples (18 schizophrenia cases and 15 controls) were obtained from Douglas Bell-Canada Brain Bank (DBCBB), Montreal, Canada. Bisulfite converted DNA from these samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip v1.0.

2014-09-13 | E-GEOD-61380 | biostudies-arrayexpress

Transcriptomic analysis of probable asymptomatic and symptomatic Alzheimer Brains

Project description:Objectives: Individuals with intact cognition and neuropathology consistent with Alzheimer’s disease (AD) are referred to as asymptomatic AD (AsymAD). These individuals are highly likely to develop AD, yet transcriptomic changes in the brain which might reveal mechanisms for their AD vulnerability are currently unknown. Methods: Differential and co-expression analysis was performed on microarray profiled human brains of 27 control , 33 AsymAD and 52 AD subjects. Tissues known to be affected by AD neuropathology (entorhinal cortex, temporal cortex, frontal cortex) and tissue partially spared by the disease (cerebellum). Results: The AsymAD subjects exhibited significant changes in transcriptomic activity in the frontal cortex when compared to AD and control subjects. Fourteen genes (GPM6B, ANKEF1, NPC2, ALDH2, FBLN2, METTL7A, FLCN, ASPHD1, ARL5A, GPR162, HBA2, PCID2, BEND3 and RAP1Gap) were highly associated with AD neuropathology with overall disturbances in the “glutamate-glutamine cycle”, “oxidative phosphorylation”, “innate immune system”, “TYROBP network”, “neutrophil degranulation” and “amino acid metabolism” in both the AsymAD and AD subjects. Conclusions: Transcriptomic activity in AsymAD subjects suggests fundamental changes in AD brains may begin within the frontal cortex region. In addition, we provide new insight into the earliest biological changes occurring in the brain prior to clinical AD diagnosis which offers new avenues for therapeutic interventions for preventing AD. We provide access of gene-level results to the broader research community through a publicly available R SHINY web-application accessible at: https://phidatalab-shiny.rosalind.kcl.ac.uk/ADbrainDE

2019-07-22 | GSE118553 | GEO

Localised protein expression changes in different regions of human Alzheimer’s brain correlate with disease severity - Sensory Cortex

Project description:Alzheimer's disease (AD) or age-matched controls (n=9/group). Mean post mortem delays were ~12h. Six distinct brain regions were dissected, Hippocampus, Cingulate Gyrus, Entorhinal Cortex (severely affected), Motor and Sensory Cortex (less affected) and Cerebellum (spared). Protein was extracted from each sample and, each region was analysed independently. For each region, samples were divided into 3 sets of 3 cases and 3 controls and assigned to an iTRAQ 8 plex, alongside two aliquots of a pooled QC sample. Samples were digested, iTRAQ labelled and analysed. For each region, between 3000 and 4200 proteins were compared between AD and control, identifying a series of known and novel protein expression changes associated with the progression of AD.

2019-02-15 | PXD008753 | Pride

Methylomic signatures of tau and beta amyloid in transgenic mouse models of Alzheimer’s disease neuropathology [RRBS]

Project description:We identified widespread DNA methylation changes associated with the development of both tau and amyloid neuropathology, including differentially methylated positions (DMPs) and regions (DMRs) at loci previously implicated in AD and overlapping changes identified in our ongoing analyses of human post-mortem AD brains.

2024-10-30 | GSE246560 | GEO

Methylomic signatures of tau and beta amyloid in transgenic mouse models of Alzheimer’s disease neuropathology [HorvathMammalMethylChip40 Methylation Beadchip]

2024-10-30 | GSE246559 | GEO

Localised protein expression changes in different regions of human Alzheimer’s brain correlate with disease severity - Motor cortex

Project description:Human brain tissue was obtained from the New Zealand Brain Bank from donors with Alzheimer's disease (AD) or age-matched controls (n=9/group). Mean post mortem delays were ~12h. Six distinct brain regions were dissected, Hippocampus, Cingulate Gyrus, Entorhinal Cortex (severely affected), Motor and Sensory Cortex (less affected) and Cerebellum (spared). Protein was extracted from each sample and, each region was analysed independently. For each region, samples were divided into 3 sets of 3 cases and 3 controls and assigned to an iTRAQ 8 plex, alongside two aliquots of a pooled QC sample. Samples were digested, iTRAQ labelled and analysed. For each region, between 3000 and 4200 proteins were compared between AD and control, identifying a series of known and novel protein expression changes associated with the progression of AD.

2019-02-15 | PXD008807 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data