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Alzheimer's disease DNA (hydroxy) methylome in the brain: OXT methylation as a preclinical marker.

ABSTRACT: The present study investigated the DNA methylome and hydroxymethylome, as well as unmodified cytosine in relation to Alzheimer’s disease (AD). We identified epigenetic differences between AD patients and age-matched controls in the middle temporal gyrus, in genomic regions associated with genes such as OXT, ACSL1, RHBDF2, C3, and MIR9-3HG. Interestingly, we found that OXT methylation in the blood of aged, non-demented individuals is also associated with conversion to AD dementia. The current GEO records concerns the middle temporal gyrus (ox)BS-processed Illumina 450K dataset of this study.

ORGANISM(S): Homo sapiens

PROVIDER: GSE109627 | GEO | 2019/12/09

REPOSITORIES: GEO

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Alzheimer’s disease DNA (hydroxy)methylome in the brain and blood: OXT methylation as a preclinical marker.

Project description:The present study investigated the DNA methylome and hydroxymethylome, as well as unmodified cytosine in relation to Alzheimer’s disease (AD). We identified epigenetic differences between AD patients and age-matched controls in the middle temporal gyrus, in genomic regions associated with genes such as OXT, ACSL1, RHBDF2, C3, and MIR9-3HG. Interestingly, we found that OXT methylation in the blood of aged, non-demented individuals is also associated with conversion to AD dementia. The current GEO submission concerns the middle temporal gyrus Illumina HumanHT-12 V4.0 expression dataset of this study that was used to look at the correlation between the detected epigenetic changes and gene expression.

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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).

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Project description:Gene expression profiling was performed on frontal and temporal cortex from vascular dementia (VaD), Alzheimer's disease (AD), and non-demented controls (Control) obtained from the University of Michigan Brain Bank. Controls and AD cases had no infarcts in the autopsied hemisphere. Vascular dementia cases had low Braak staging.

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Project description:We used label-free shotgun mass spectrometry to analyze temporal neocortex samples from AD brain, other neurological disorders and non-demented controls, in order to identify additional proteins thatare altered in AD. The mass spectrometry results were then verified by antibody suspension bead arrays.

2016-09-29 | PXD004499 | Pride

Transcriptome changes in the Alzheimer's middle temporal gyrus: importance of RNA metabolism and mitochondria-associated membrane (MAM) genes

Project description:We used Illumina Human HT-12 v4 arrays to compare RNA expression of middle temporal gyrus (MTG; BA21) in Alzheimer’s Disease (AD = 97) and non-demented controls (ND = 98). A total of 938 transcripts were highly differentially expressed (adj p < 0.01; log2 Fold Change (FC) ≥ |0.500|, with 411 overexpressed and 527 underexpressed in AD. Our results correlated with expression profiling in neurons from AD and ND obtained by Laser Capture Microscopy in MTG from an independent dataset (log2 FC correlation: r = 0.504; p = 2.2e-16). Additionally selected effects were validated by qPCR. ANOVA analysis yielded no difference between genders in response to AD, but some gender specific genes were detected (e.g: IL8 and AGRN in males, and HSPH1 and GRM1 in females). Several transcripts were associated with Braak Staging (e.g AEBP1 and DNALI1), ante-mortem MMSE (e.g. AEBP1 and GFAP) and Tangle density (eg. RNU1G2, and DNALI1). At the pathway level we detected enrichment of Synaptic Vesicle Processes and GABAergic transmission genes. Finally, applying the Weighted Correlation Network Analysis (WGCNA) we identified 4 expression modules enriched for neuronal and synaptic genes, mitochondria-associated membrane (MAM), chemical stimulus and olfactory receptor and non-coding RNA metabolism genes. Our results represent an extensive description of MTG mRNA profiling in a large sample of AD and ND. These data provide a list of genes associated with AD, and correlated to neurofibrillary tangles density. In addition, these data emphasize the importance of mitochondrial membranes and transcripts related to olfactory receptors in AD.

2019-06-19 | GSE132903 | GEO

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