Transcriptomic analysis of probable asymptomatic and symptomatic Alzheimer Brains
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ABSTRACT:
PROVIDER: PRJNA486003 | ENA |
REPOSITORIES: ENA
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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
Project description:Alterations of protein abundance and post-translational modifications in patients with Alzheimer’s disease (AD), such as glycosylation, phosphorylation, and ubiquitination, and their roles in disease progression and treatment outcome are areas of intense study. Little is known, however, about the overall N-glycosylation of proteins in human brains, and those from Alzheimer’s patients, particularly in regard to large-scale intact N-linked glycoproteomics analysis. To elucidate the glycoproteome landscape, we developed an approach based on multi-lectin affinity enrichment, hydrophilic interaction chromatography (HILIC), and LC-MS-based glycoproteomics analysis. We analyzed 10 normal, 10 asymptomatic, and 10 symptomatic AD brains, in which we detected >300 glycoproteins and >1,900 glycoforms across the samples. The majority of glycoproteins have N-glycans that are high-mannosidic and complex chains that are fucosylated and bisected. The Man5 N-glycan was found to occur most frequently at >20% of the total glycoforms. Unlike the glycoproteomes of other tissues, sialylation is a minor feature of the brain glycoproteome, occurring at <9% of N-glycans . We observed changes in the number of antennae, frequency of fucosylation, bisection, and other monosaccharides at individual glycosylation sites among normal, asymptomatic, and symptomatic AD samples. Further analysis revealed glycosylation differences in subcellular compartments. We did not observe a statistical difference between male and female patients. These results represent the first glycoproteomics landscape of brains from multiple AD individuals, which will facilitate a deeper understanding of AD and possible disease treatment options.
2022-10-31 | PXD032219 | Pride
Project description:We compared gene expression profiles between asymptomatic and symptomatic atherosclerotic plaques from the same patient. This was accomplished by analyzing carotid plaques from four patients with bilateral high-grade carotid artery stenoses one being symptomatic (TIA or stroke) and the other asymptomatic.
2006-02-10 | E-MEXP-268 | biostudies-arrayexpress
Project description:Domoic acid (DA) is a neuroexcitatory amino acid that is naturally produced by some marine diatom species of the genus Pseudo-nitzschia. Ingestion of DA-contaminated seafood by humans results in a severe neurotoxic disease known as amnesic shellfish poisoning (ASP). Clinical signs of ASP include seizures and neuronal damage from activation of AMPA and kainate receptors. However, the impacts of DA exposure at levels below those known to induce outward signs of neurobehavioral exicitotoxicity have not been well characterized. To further understand the mechanisms of neurotoxic injury associated with DA exposure, we examined the transcriptome of whole brains from zebrafish (Danio rerio) receiving intracoelomic (IC) DA at both symptomatic and asymptomatic doses. A majority of zebrafish exposed to high-dose DA (1.2 µg DA/g) exhibited clinical signs of neuroexcitotoxicity (EC50 of 0.86 µg DA/g) within 5 to 20 minutes of IC injection. All zebrafish receiving low-dose DA (0.47 µg DA/g) or vehicle only maintained normal behavior. Microarray analysis of symptomatic and asymptomatic exposures collectively yielded 306 differentially expressed genes (1.5-fold, p = 0.05) predominately represented by signal transduction, ion transport, and transcription factor functional categories. Transcriptional profiles were suggestive of neuronal apoptosis following an overwhelming of protective adaptive pathways. Further, potential molecular biomarkers of neuropathic injury, including Nrdg4, were identified and may be relevant to DA exposure levels below that causing neurobehavioral injury. Our results validate zebrafish as a vertebrate model to study mechanisms of DA neurotoxicity and provide a basis for identifying pathways of DA-induced injury as well as biomarkers of asymptomatic and symptomatic DA exposure levels. Keywords: neurotoxic disease To further understand the mechanisms of neurotoxic injury associated with DA exposure, we examined the transcriptome of whole brains from zebrafish (Danio rerio) receiving intracoelomic (IC) DA at both symptomatic and asymptomatic doses. A majority of zebrafish exposed to high-dose DA (1.2 µg DA/g) exhibited clinical signs of neuroexcitotoxicity (EC50 of 0.86 µg DA/g) within 5 to 20 minutes of IC injection. All zebrafish receiving low-dose DA (0.47 µg DA/g) or vehicle only maintained normal behavior. Microarray analysis of symptomatic and asymptomatic exposures collectively yielded 306 differentially expressed genes (1.5-fold, p = 0.05) predominately represented by signal transduction, ion transport, and transcription factor functional categories. All animal studies were carried out under approved IACUC protocols at the University of Washington.
2009-07-06 | E-GEOD-12140 | biostudies-arrayexpress
Project description:To exploite S. sclerotiorum to identify differential fungal responses leading to either an endophytic or a pathogenic lifestyle during colonization of both asymptomatic host and symptomatic host We then performed gene expression profiling analysis using data obtained from RNA-seq of 9 different samples after 2 days.
2023-10-09 | GSE218908 | GEO
Project description:Human rhinoviruses (HRV) are among the most common causes of respiratory infections in humans but can be frequently detected also in asymptomatic subjects. We evaluated the value of gene expression profiles to differentiate asymptomatic detection from symptomatic HRV infection in children.
2016-01-14 | GSE67059 | GEO
Project description:This study investigates how the baseline expression level of genes impact symptomatic outcome of flaviviral infection. Before given the YF17D vaccine, whole blood was extracted into tempus tubes from vaccinated subjects. Thereafter, the subjects were assessed if they experienced adverse events (or symptoms). 35 subjects (n=12 symptomatic, n=23 asymptomatic) were processed according to manufacturer's protocol. Transcript expression was then evaluated by nCounter RNA Cancer Metabolism (#VRXC-CM1-12) or a custom Unfolded Protein Response codeset and its respective probesets.
2019-05-11 | E-MTAB-7931 | biostudies-arrayexpress
Project description:This study investigates how the baseline expression level of genes impact symptomatic outcome of flaviviral infection. Before given the YF17D vaccine, whole blood was extracted into tempus tubes from vaccinated subjects. Thereafter, the subjects were assessed if they experienced adverse events (or symptoms). 27 subjects (n=19 symptomatic, n=8 asymptomatic) were processed according to manufacturer's protocol. Transcript expression was then evaluated by Affymetrix Human GeneChip 2.0 ST array, performed at Duke-NUS Genome Biology Core Facility. Data analysis and processing was performed using Partek software and enriched pathways determined by Reactome database from Enrichr.
2019-05-11 | E-MTAB-7928 | biostudies-arrayexpress
Project description:Sclerotinia sclerotiorum responses to symptomatic versus asymptomatic host
| PRJNA906117 | ENA
Project description:Domoic acid (DA) is a neuroexcitatory amino acid that is naturally produced by some marine diatom species of the genus Pseudo-nitzschia. Ingestion of DA-contaminated seafood by humans results in a severe neurotoxic disease known as amnesic shellfish poisoning (ASP). Clinical signs of ASP include seizures and neuronal damage from activation of AMPA and kainate receptors. However, the impacts of DA exposure at levels below those known to induce outward signs of neurobehavioral exicitotoxicity have not been well characterized. To further understand the mechanisms of neurotoxic injury associated with DA exposure, we examined the transcriptome of whole brains from zebrafish (Danio rerio) receiving intracoelomic (IC) DA at both symptomatic and asymptomatic doses. A majority of zebrafish exposed to high-dose DA (1.2 µg DA/g) exhibited clinical signs of neuroexcitotoxicity (EC50 of 0.86 µg DA/g) within 5 to 20 minutes of IC injection. All zebrafish receiving low-dose DA (0.47 µg DA/g) or vehicle only maintained normal behavior. Microarray analysis of symptomatic and asymptomatic exposures collectively yielded 306 differentially expressed genes (1.5-fold, p = 0.05) predominately represented by signal transduction, ion transport, and transcription factor functional categories. Transcriptional profiles were suggestive of neuronal apoptosis following an overwhelming of protective adaptive pathways. Further, potential molecular biomarkers of neuropathic injury, including Nrdg4, were identified and may be relevant to DA exposure levels below that causing neurobehavioral injury. Our results validate zebrafish as a vertebrate model to study mechanisms of DA neurotoxicity and provide a basis for identifying pathways of DA-induced injury as well as biomarkers of asymptomatic and symptomatic DA exposure levels. Keywords: neurotoxic disease
2009-07-06 | GSE12140 | GEO