Identification of Differential Genes of DNA Methylation Associated With Alzheimer’s Disease Based on Integrated Bioinformatics and Its Diagnostic Significance DOI Creative Commons
Fan Chen, Na Wang, Xiaping He

et al.

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: May 9, 2022

Alzheimer's disease (AD) is a common neurodegenerative disease. The pathogenesis complex and has not been clearly elucidated, there no effective treatment. Recent studies have demonstrated that DNA methylation closely associated with the of AD, which sheds light on investigating potential biomarkers for diagnosis early AD related possible therapeutic approaches.Alzheimer's patients samples healthy controls were collected from two datasets in GEO database. Using LIMMA software package R language to find differentially expressed genes (DEGs). Afterward, DEGs subjected enrichment analysis GO KEGG pathways. PPI networks Hub created visualized based STRING database Cytoscape. ROC curves further constructed analyze accuracy these diagnosis.Analysis GSE109887 GSE97760 showed 477 significant DEGs. terms biological processes genes. top ten found basis network using CytoHubba plugin, AUC areas ranked all greater than 0.7, showing satisfactory diagnostic accuracy.The study identified 10 AD-related methylation, RPSA, RPS23, RPLP0 high excellent biomarker potential.

Language: Английский

Upregulation of ribosome complexes at the blood-brain barrier in Alzheimer's disease patients DOI

Masayoshi Suzuki,

Kenta Tezuka,

Takumi Handa

et al.

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2022, Volume and Issue: 42(11), P. 2134 - 2150

Published: June 29, 2022

The cerebrovascular-specific molecular mechanism in Alzheimer’s disease (AD) was investigated by employing comprehensive and accurate quantitative proteomics. Highly purified brain capillaries were isolated from cerebral gray white matter of four AD three control donors, examined SWATH (sequential window acquisition all theoretical fragment ion spectra) Of the 29 ribosomal proteins that quantified, 28 (RPLP0, RPL4, RPL6, RPL7A, RPL8, RPL10A, RPL11, RPL12, RPL14, RPL15, RPL18, RPL23, RPL27, RPL27A, RPL31, RPL35A, RPS2, RPS3, RPS3A, RPS4X, RPS7, RPS8, RPS14, RPS16, RPS20, RPS24, RPS25, RPSA) significantly upregulated patients. This upregulation protein expression occurred only not parenchyma. processing N-glycosylation-related endoplasmic reticulum (DDOST, STT3A, MOGS, GANAB, RPN1, RPN2, SEC61B, UGGT1, LMAN2, SSR4) also correlated with proteins. findings reported herein indicate ribosome complex, subsequent processes are specifically

Language: Английский

Citations

46
Porphyromonas gingivalis Outer Membrane Vesicles as the Major Driver of and Explanation for Neuropathogenesis, the Cholinergic Hypothesis, Iron Dyshomeostasis, and Salivary Lactoferrin in Alzheimer’s Disease DOI Creative Commons

Peter L. Nara,

Daniel Sindelar,

Marc S. Penn

et al.

Journal of Alzheimer s Disease, Journal Year: 2021, Volume and Issue: 82(4), P. 1417 - 1450

Published: July 16, 2021

Porphyromonas gingivalis (Pg) is a primary oral pathogen in the widespread biofilm-induced "chronic" multi-systems inflammatory disease(s) including Alzheimer's disease (AD). It possibly only second identified unique example of biological extremophile human body. Having better understanding key microbiological and genetic mechanisms its pathogenesis induction are central to future diagnosis, treatment, possible prevention. The published literature around role Pg AD highlights bacteria's direct within brain cause disease. available evidence, although somewhat adopted, does not fully support this as major process. There alternative pathogenic/virulence features associated with that have been overlooked may explain pathogenic processes found "infection hypothesis" AD. A explanation offered here for discrepancy relatively low amounts "Pg bacteria" residing compared rather florid broad distribution one or more bacterial protein toxins. Related this, "Gingipains Hypothesis", AD-related iron dyshomeostasis, early reduced salivary lactoferrin, along resurrection Cholinergic Hypothesis now be integrated into working model. current paper suggests highly evolved developed Type IX secretory cargo system producing outer membrane vesicles observed diseases. Thus it hoped can provide unifying model sporadic form guide direction research,

Language: Английский

Citations

46
A single-cell atlas to map sex-specific gene-expression changes in blood upon neurodegeneration DOI Creative Commons
Friederike Grandke, Tobias Fehlmann, Fabian Kern

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 25, 2025

Abstract The clinical course and treatment of neurodegenerative disease are complicated by immune-system interference chronic inflammatory processes, which remain incompletely understood. Mapping immune signatures in larger human cohorts through single-cell gene expression profiling supports our understanding observed peripheral changes neurodegeneration. Here, we employ over 909k blood mononuclear cells (PBMCs) from 121 healthy individuals, 48 patients with mild cognitive impairment (MCI), 46 Parkinson’s (PD), 27 Alzheimer’s (AD), 15 both PD MCI. dataset is interactively accessible a freely available website ( https://www.ccb.uni-saarland.de/adrcsc ). In this work, identify disease-associated cell type composition the sex-specific manner, offering insights into solid tissue AD PD.

Language: Английский

Citations

0
Characterization of Human Genes Modulated by Porphyromonas gingivalis Highlights the Ribosome, Hypothalamus, and Cholinergic Neurons DOI Creative Commons
Sejal Patel, Derek Howard, Nityananda Chowdhury

et al.

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: June 14, 2021

, a bacterium associated with periodontal disease, is suspected cause of Alzheimer's disease. This reliant on gingipain proteases, which cleave host proteins after arginine and lysine residues. To characterize susceptibility, we performed enrichment analyses proportion proteome-wide. Genes differentially expressed in brain samples detected

Language: Английский

Citations

26
The Caribbean-Hispanic Alzheimer's disease brain transcriptome reveals ancestry-specific disease mechanisms DOI Creative Commons
Daniel Felsky, Ismael Santa‐María, Mehmet İlyas Coşacak

et al.

Neurobiology of Disease, Journal Year: 2022, Volume and Issue: 176, P. 105938 - 105938

Published: Nov. 30, 2022

Identifying ancestry-specific molecular profiles of late-onset Alzheimer's Disease (LOAD) in brain tissue is crucial to understand novel mechanisms and develop effective interventions non-European, high-risk populations. We performed gene differential expression (DE) consensus network-based analyses RNA-sequencing data postmortem from 39 Caribbean Hispanics (CH). To identify ancestry-concordant -discordant profiles, we compared our results those two independent non-Hispanic White (NHW) samples (n = 731). In CH, identified 2802 significant DE genes, including several LOAD known-loci. effects were highly concordant across ethnicities, with 373 genes transcriptome-wide all three cohorts. Cross-ancestry meta-analysis found NPNT be the top gene. replicated over 82% meta-analyses genome-wide signals single-nucleus RNA-seq (including known-genes SORL1, FBXL7, CLU, ABCA7). Increasing representation genetic studies will allow for deeper understanding improving precision treatment options understudied groups.

Language: Английский

Citations

18
MousiPLIER: A Mouse Pathway-Level Information Extractor Model DOI Creative Commons
Shuo Zhang, Benjamin J. Heil, Weiguang Mao

et al.

eNeuro, Journal Year: 2024, Volume and Issue: 11(6), P. ENEURO.0313 - 23.2024

Published: May 24, 2024

High-throughput gene expression profiling measures individual across conditions. However, genes are regulated in complex networks, not as entities, limiting the interpretability of data. Machine learning models that incorporate prior biological knowledge a powerful tool to extract meaningful biology from Pathway-level information extractor (PLIER) is an unsupervised machine method defines pathways by leveraging vast amount published transcriptomic PLIER converts data into known pathway sets, termed latent variables (LVs), substantially reduce dimensionality and improve interpretability. In current study, we trained first mouse model on 190,111 brain RNA-sequencing samples, greatest training ever used PLIER. We then validated mousiPLIER approach study microglia astrocyte aging. identified significantly associated with aging, including one variable (LV41) corresponding striatal signal. To gain further insight contained LV41, performed k-means clustering identify studies respond strongly LV41. found was relevant striatum aging scientific literature. Finally, built Web server (http://mousiplier.greenelab.com/) for users easily explore learned variables. Taken together, this uncover processes studies.

Language: Английский

Citations

1
Novel Insights into Changes in Gene Expression within the Hypothalamus in Two Asthma Mouse Models: A Transcriptomic Lung–Brain Axis Study DOI Open Access
Eslam M. Bastawy, Izel M. Eraslan, Lara M. Voglsanger

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7391 - 7391

Published: July 5, 2024

Patients with asthma experience elevated rates of mental illness. However, the molecular links underlying such lung-brain crosstalk remain ambiguous. Hypothalamic dysfunction is observed in many psychiatric disorders, particularly those an inflammatory component due to hypothalamic regions being unprotected by blood-brain barrier. To gain a better insight into neuropsychiatric sequelae, this study investigated gene expression differences hypothalamus following lung inflammation (asthma) induction mice, using RNA transcriptome profiling. BALB/c mice were challenged either bacterial lipopolysaccharide (LPS, E. coli) or ovalbumin (OVA) allergens saline control (n = 7 per group), and was confirmed via histological examination postmortem tissue. The majority micro-dissected, total extracted for sequencing. Differential analysis identified 31 statistically significant single genes (false discovery rate FDR5%) altered LPS exposure compared controls; however, none significantly changed OVA treatment, suggesting milder response. When sets examined, 48 upregulated 8 downregulated both groups relative controls. REACTOME enrichment suggests these are involved signal transduction metabolism, immune response neuroplasticity. Interestingly, we five directly associated neurotransmitter signaling. Intriguingly, can influence health or/neuroinflammation humans. These findings help characterize between asthma-induced brain may assist identifying relevant pathways therapeutic targets future intervention.

Language: Английский

Citations

1
Identification of Differential Genes of DNA Methylation Associated With Alzheimer’s Disease Based on Integrated Bioinformatics and Its Diagnostic Significance DOI Creative Commons
Fan Chen, Na Wang, Xiaping He

et al.

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: May 9, 2022

Alzheimer's disease (AD) is a common neurodegenerative disease. The pathogenesis complex and has not been clearly elucidated, there no effective treatment. Recent studies have demonstrated that DNA methylation closely associated with the of AD, which sheds light on investigating potential biomarkers for diagnosis early AD related possible therapeutic approaches.Alzheimer's patients samples healthy controls were collected from two datasets in GEO database. Using LIMMA software package R language to find differentially expressed genes (DEGs). Afterward, DEGs subjected enrichment analysis GO KEGG pathways. PPI networks Hub created visualized based STRING database Cytoscape. ROC curves further constructed analyze accuracy these diagnosis.Analysis GSE109887 GSE97760 showed 477 significant DEGs. terms biological processes genes. top ten found basis network using CytoHubba plugin, AUC areas ranked all greater than 0.7, showing satisfactory diagnostic accuracy.The study identified 10 AD-related methylation, RPSA, RPS23, RPLP0 high excellent biomarker potential.

Language: Английский

Citations

6