Cortex DNA methylation profiles for the Brains for Dementia research cohort
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ABSTRACT:
PROVIDER: PRJNA809726 | ENA |
REPOSITORIES: ENA
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Project description:Genome-wide patterns of DNA methylation were quantified using the Illumina Infinium HumanMethylationEPIC BeadChip (“EPIC array”) in DNA samples isolated from cortex (dorsolateral prefrontal cortex and occipital cortex) for individuals with various amounts of dementia neuropathology.
2022-06-27 | GSE197305 | GEO
Project description:We investigated transcriptome alterations in the prefrontal cortex (BA) of patients with Alzheimer’s disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) when compared with elderly controls without neurological or psychiatric diseases (CTRL) using Affymetrix Human Transcriptome Array 2.0 All brain samples were provided by the Brains for Dementia Research (BDR), UK. All cases were prospectively assessed by experienced clinicians using validated clinical rating instruments. The samples processed in each group were matched for age, sex and postmortem interval (PMI) as far as possible.
2021-05-24 | GSE150696 | GEO
Project description:Aggregated α-synuclein (α-SYN) proteins, encoded by the SNCA gene, are hallmarks of Lewy body disease (LBD), affecting multiple brain regions. However, the specific mechanisms underlying α-SYN pathology in cortical neurons, crucial for LBD-associated dementia, remain unclear. Here, we generated human cortical LBD models by differentiating induced pluripotent stem cells (iPSCs) from SNCA triplication LBD patients into cerebral organoids and observed increased levels of pathological α-SYN in these organoids. Single-cell RNA sequencing revealed prominent expression of the SNCA gene in excitatory neurons, which exhibited synaptic and mitochondrial dysfunction, consistent with findings in the cortex of LBD human brains. Furthermore, screening 1280 FDA-approved drugs identified four candidates, which inhibited α-SYN seeding in RT-QuIC assay, reduced α-SYN aggregation and alleviated mitochondrial dysfunction in SNCA triplication iPSC models. Our findings provide valuable insights into the development of cortical LBD models and the discovery of potential drugs targeting α-SYN aggregation.
2024-09-18 | GSE235914 | GEO
Project description:Objective. The goal of this study was to examine the microRNA (miRNA) profile of Parkinsonâ??s disease (PD) frontal cortex as compared to normal control brain, allowing for the identification of PD specific signatures as well as the study of disease-related phenotypes, such as onset age or dementia Methods. Small RNA sequence analysis was performed from prefrontal cortex for 29 PD samples and 33 control samples. After sample QC, normalization and batch correction, linear regression was used to identify miRNAs altered in PD, and a PD classifier was developed using weighted voting class prediction. The relationship of miRNA levels to onset age and PD with dementia (PDD) was also characterized in case-only analyses. Results. 125 miRNAs were differentially expressed in PD at a genome-wide level of significance (FDR q<0.05). A set of 29 miRNAs classified PD from non-diseased brain (93.9% specificity, 96.6% sensitivity). The majority of differentially expressed miRNAs (105/125) showed an ordinal relationship from control, to PD without dementia (PDN), to PDD. Among PD brains, 36 miRNAs classified PDD from PDN (sensitivity =81.2%, specificity =88.9%). Among differentially expressed miRNAs, miR-10b-5p had a positive association with onset age (q=4.7e-2). Conclusions. Based on cortical miRNA levels, PD brains were accurately classified from non-diseased brains. Additionally, the PDD miRNA profile exhibited a more severe pattern of alteration among those differentially expressed in PD. To evaluate the clinical utility of miRNAs as potential clinical biomarkers, further characterization and testing of brain-related miRNA alterations in peripheral biofluids is justified. 29 Parkinson's disease prefrontal cortex samples analyzed with 33 control samples from Series GSE64977.
2016-03-16 | E-GEOD-72962 | biostudies-arrayexpress
Project description:Mapping genotype-expression associations in Heterogeneous Stock rat brains to advance behavioral genetics research [Orbitofrontal cortex]
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Project description:To identify molecular pathological alterations in AD brains, we performed interspecies comparative microarray analyses using RNAs prepared from postmortem human brain tissues donated for the Hisayama study and hippocampal RNAs from the triple-transgenic mouse model of AD (3xTg-AD) Three-way ANOVA of microarray data from frontal cortex, temporal cortex and hippocampus with presence/absence of AD and vascular dementia, and sex, as factors revealed that the gene expression profile is most significantly altered in the hippocampi of AD brains. Comparative analyses of the brains of AD patients and a mouse model of AD showed that genes involved in non-insulin dependent DM and obesity were significantly altered in both, as were genes related to psychiatric disorders and Alzheimer’s disease. We prepared RNA samples from the gray matter of frontal and temporal cortices and hippocampi derived from 88 postmortem brains, among which 26 cases were pathologically diagnosed as having AD or an AD-like disorder. High-quality RNA (RIN≧6.9) samples were subjected to microarray analysis using the Affymetrix Human Gene 1.0 ST platform, and only those results that passed examinations for quality assurance and quality control of the Human Gene 1.0 ST arrays were retrieved. In total, we obtained gene expression profiles from the following samples: 33 frontal cortex samples, among which 15 were from AD patients; 29 temporal cortex samples, among which 10 were from AD patients; 17 hippocampus samples, among which seven were from AD patients
2013-04-17 | E-GEOD-36980 | biostudies-arrayexpress
Project description:Single nucleus RNA sequencing data of Lewy Body Dementia (LBD) brains
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Project description:To identify molecular pathological alterations in AD brains, we performed interspecies comparative microarray analyses using RNAs prepared from postmortem human brain tissues donated for the Hisayama study and hippocampal RNAs from the triple-transgenic mouse model of AD (3xTg-AD) Three-way ANOVA of microarray data from frontal cortex, temporal cortex and hippocampus with presence/absence of AD and vascular dementia, and sex, as factors revealed that the gene expression profile is most significantly altered in the hippocampi of AD brains. Comparative analyses of the brains of AD patients and a mouse model of AD showed that genes involved in non-insulin dependent DM and obesity were significantly altered in both, as were genes related to psychiatric disorders and Alzheimer’s disease.
2013-04-17 | GSE36980 | GEO