Methylation profiling by array for Dementia with Lewy Bodies using brain tissue
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PROVIDER: PRJNA1139675 | ENA |
REPOSITORIES: ENA
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Project description:Synucleinopathies encompass Parkinsons disease (PD), dementia with Lewy bodies (DLB), and Parkinsons disease dementia (PDD) and are recognized for presenting a range of cognitive, neuropsychiatric, sleep-related, motor, and autonomic symptoms. DLB manifests with early-onset dementia when Lewy bodies develop in the brainstem and cerebral cortex. We profiled the DNA methylation using the post-mortem brain tissue from the parietal cortex, specifically Brodmann area 7 and compared them with age-, and sex-matched controls. Through the integration of multi-omics approaches, we anticipate the identification of notable alterations in these well-defined samples. Additionally, our objective is to study the biochemical perturbations in the brain tissue of those individuals who died with DLB. Differentially Methylated Cytosines (DMCs) and metabolites were identified, followed by pathway enrichment analysis. Correlations between methylation changes and metabolite levels were explored. Methylation profiling revealed 3,478 significant DMCs, predominantly hypermethylated, enriched in CpG islands and gene regions related to transcription start sites. Pathway analysis identified 612 significant pathways, with notable involvement in olfactory and synaptic functions. Metabolomics profiling identified 15 significantly differentially abundant metabolites. The top perturbed pathway was Phosphatidylethanolamine (PE) Biosynthesis. Further, key correlations were found between significant DMCs and metabolites, particularly in the Phosphatidylethanolamine Biosynthesis pathway involving genes PTDSS1 and PCYT2. Further, ignsificant sex-specific epigenetic and metabolomic changes were also observed. This comprehensive analysis of DNA methylation and metabolomics in DLB highlights significant biomarkers and pathways, offering insights into disease mechanisms and potential therapeutic targets.
2025-01-15 | GSE272947 | GEO
Project description:Proteomic analysis were performed in olfactory bulbs derived from controls and individuals with dementia with lewy bodies
2021-09-08 | PXD016069 | Pride
Project description:MicroRNAs (miRNAs) are small (20-22 nucleotides) regulatory non-coding RNAs that strongly influence gene expression. Most prior studies addressing the role of miRNAs in neurodegenerative diseases (NDs) have focused on individual controls (n = 2), AD (n = 5), dementia with Lewy bodies (n = 4), hippocampal sclerosis of aging (n = 4), and frontotemporal lobar dementia (FTLD) (n = 5) cases, together accounting for the most prevalent ND subtypes. All cases had short postmortem intervals, relatively high-quality RNA, and state-of-the-art neuropathological diagnoses. The resulting data (over 113 million reads in total, averaging 5.6 million reads per sample) and secondary expression analyses constitute an unprecedented look into the human cerebral cortical miRNome at single nucleotide resolution. While we find no apparent changes in isomiR or miRNA editing patterns in correlation with ND pathology, our results validate and extend previous miRNA profiling studies with regard to quantitative changes in NDs. In agreement with this idea, we provide independent cohort validation for changes in miR-132 expression levels in AD (n = 8) and FTLD (n = 14) cases when compared to controls (n = 8). The identification of common and ND-specific putative novel brain miRNAs and/or short-hairpin molecules is also presented. The challenge now is to better understand the impact of these and other alterations on neuronal gene expression networks and neuropathologies. Using RNA deep sequencing, we sought to analyze in detail the small RNAs (including miRNAs) in the temporal neocortex gray matter from non-demented controls (n = 2), AD (n = 5), dementia with Lewy bodies (n = 4), hippocampal sclerosis of aging (n = 4), and frontotemporal lobar dementia (FTLD) (n = 5) cases, together accounting for the most prevalent ND subtypes.
2013-04-18 | E-GEOD-46131 | biostudies-arrayexpress
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:Dementia with Lewy bodies (DLB) is a common form of dementia with known genetic and environmental interactions. However, the underlying epigenetic mechanisms which reflect these gene-environment interactions are poorly studied. Herein, we measured genome-wide DNA methylation profiles of post-mortem brain tissue (Broadmann area 7) from 15 pathologically confirmed DLB brains and compared them with 16 cognitively normal controls using Illumina MethylationEPIC arrays. We identified 17 significantly differentially methylated CpGs (DMCs) and 17 differentially methylated regions (DMRs) between the groups. The DMCs are mainly located at the CpG islands, promoter and first exon regions. Genes associated with the DMCs are linked to “Parkinson disease” and “metabolic pathway”, as well as the diseases of “severe intellectual disability” and “mood disorders”. Overall, our study highlights previously unreported DMCs offering insights into DLB pathogenesis with the possibility that some of these could be used as biomarkers of DLB in the future.
2022-09-08 | GSE190348 | GEO
Project description:Recent studies indicate a role of the adaptive immune system in Lewy body dementia (LBD). However, the mechanisms regulating T cell brain homing in LBD remain unknown. Here, we demonstrate interaction of T cells with Lewy bodies and with dopaminergic neurons in post-mortem LBD brains. Single cell RNA sequencing of cerebrospinal fluid (CSF) cells identified upregulated expression of C-X-C Motif Chemokine Receptor 4 (CXCR4) in CD4+ T cells in LBD. CSF protein levels of the CXCR4 ligand, C-X-C Motif Chemokine Ligand 12 (CXCL12) were associated with neuroaxonal damage in LBD. Finally, we demonstrate clonal expansion and upregulated Interleukin 17A by CD4+ T cells stimulated with phosphorylated α-synuclein. Cumulatively, these results indicate CXCR4-CXCL12 signaling as a mechanistic target for inhibiting pathological T cell trafficking in LBD.
2021-09-14 | GSE161192 | GEO
Project description:Recent studies indicate that the adaptive immune system plays a role in Lewy body dementia (LBD). However, the mechanism regulating T cell brain homing in LBD is unknown. Here, we observed T cells adjacent to Lewy bodies and dopaminergic neurons in post-mortem LBD brains. Single-cell RNA sequencing of cerebrospinal fluid (CSF) identified upregulated expression of C-X-C Motif Chemokine Receptor 4 (CXCR4) in CD4+ T cells in LBD. CSF protein levels of the CXCR4 ligand, C-X-C Motif Chemokine Ligand 12 (CXCL12) were associated with neuroaxonal damage in LBD. Furthermore, we observed clonal expansion and upregulated Interleukin 17A expression by CD4+ T cells stimulated with a phosphorylated α-synuclein epitope. Thus, CXCR4-CXCL12 signaling may represent a mechanistic target for inhibiting pathological interleukin-17-producing T cell trafficking in LBD.
2021-09-14 | GSE141578 | GEO
Project description:Dementia with Lewy bodies post-mortem brains reveal differentially methylated CpG sites with biomarker potential
| PRJNA786798 | ENA
Project description:Dementia with Lewy bodies (DLB) is the second most common cause of degenerative dementia after Alzheimer’s disease (AD) and presents several overlapping pathological and clinical features with both AD and Parkinson’s disease (PD). Consequently, only one in three DLB cases is diagnosed correctly. Platelets are anucleate cells containing cellular structures and molecules, such as microRNA (miRNA), the analysis of which provides biomarkers for several disorders. In this cross-sectional study, we profiled the whole platelet miRNA transcriptome from 7 DLB patients and 7 healthy controls using Next-Generation Sequencing (NGS) and found 22 differentially expressed miRNAs. These miRNAs were further validated with miRCURY LNA miRNA Custom PCR panels in three consecutive validation studies carried out from 2017-2019 with a total of 162 individuals including DLB (n=59), AD (n=28), and PD patients (n=24), and healthy controls (n=51). As a result, three different groups of miRNAs were identified as related to DLB, AD and PD, all in comparison with controls. Additionally, our results demonstrated a significant down-regulation of hsa-miR-26b-5p and hsa-miR-150-5p in DLB compared to PD; and a signature composed of seven miRNAs that had lower expression in DLB compared to AD. The predictive diagnostic value of this bio-signature for the differentiation of DLB from AD was assessed calculating the corresponding ROC curve, which yielded an area under the curve of 1.00. Predictive analyses using specialized software (miRTarbase, miRGate) were performed for the disease-specific miRNAs to identify target genes and corresponding pathways. Three disease-specific clusters of pathways and biological processes were identified as a result of platelet-miRNA deregulation. In DLB, pathways related to gene expression and small RNA metabolism; in AD, pathways related to stress response and RNA stress granules; and in PD pathways related to protein phosphorylation, and protein metabolism and degradation were identified. In conclusion, we describe the identification of a novel, highly specific and sensitive platelet-associated miRNA-based bio-signature, which permits us to distinguish between DLB and AD.
2020-07-01 | GSE147218 | GEO
Project description:Human cerebrospinal fluid was collected from patients diagnosed with neurodegenerative diseases including multiple system atrophy (n=28), Parkinson’s disease (n=40), dementia with Lewy bodies (n=20), progressive supranuclear palsy (n=39) and from controls (n=17) in order to perform a comparative quantitative proteome profiling of cerebrospinal fluids from the five groups.
2022-08-12 | PXD026802 | Pride