Correction to: Exploring the potential of the platelet membrane proteome as a source of peripheral biomarkers for Alzheimer's disease.
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ABSTRACT:
SUBMITTER: Donovan LE
PROVIDER: S-EPMC8132386 | biostudies-literature | 2021 May
REPOSITORIES: biostudies-literature
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Correction to: Exploring the potential of the platelet membrane proteome as a source of peripheral biomarkers for Alzheimer's disease.
Donovan Laura E LE Dammer Eric B EB Duong Duc M DM Hanfelt John J JJ Levey Allan I AI Seyfried Nicholas T NT Lah James J JJ
Alzheimer's research & therapy 20210518 1
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Project description:Background:Alzheimer's Disease (AD) is the most common form of dementia in the elderly. Due to the facts that biological causes of AD are complex in addition to increasing rates of AD worldwide, a deeper understanding of AD etiology is required for AD treatment and diagnosis. Methods:To identify molecular pathological alterations in AD brains, GSE36980 series containing microarray data samples from temporal cortex, frontal cortex and hippocampus were downloaded from Gene Expression Omnibus (GEO) database and valid gene symbols were subjected to building a gene co-expression network by a bioinformatics tool known as differential regulation from differential co-expression (DCGL) software package. Then, a network-driven integrative analysis was performed to find significant genes and underlying biological terms. Results:A total of 17088 unique genes were parsed into three independent differential co-expression networks. As a result, a small number of differentially co-regulated genes mostly in frontal and hippocampus lobs were detected as potential biomarkers related to AD brains. Ultimately differentially co-regulated genes were enriched in biological terms including response to lipid and fatty acid and pathways mainly signaling pathway such as G-protein signaling pathway and glutamate receptor groups II and III. By conducting co-expression analysis, our study identified multiple genes that may play an important role in the pathogenesis of AD. Conclusion:The study aimed to provide a systematic understanding of the potential relationships among these genes and it is hoped that it could aid in AD biomarker discovery.
| S-EPMC6252023 | biostudies-other
Project description:IntroductionWe analyzed relationships among peripheral immunity markers, cognition, Alzheimer's disease (AD)-related biomarkers, and neuroimaging to understand peripheral immunity involvement in AD.MethodsPeripheral immunity markers were assessed in AD, non-AD neurodegenerative disorders, and controls, examining their connections with cognition, AD-related biomarkers, and neuroimaging using multiple regression models.ResultsThe study included 1579 participants. Higher levels of white blood cell, neutrophil, monocyte, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and lower lymphocyte-to-monocyte ratio (LMR) were associated with cognitive decline and more severe anxiety and depression. The impact of lower LMR, lymphocyte count, and higher NLR on cognitive decline is mediated through cerebrospinal fluid amyloid beta (Aβ) levels. Additionally, increased PLR, NLR, and SII were associated with brain atrophy and hippocampal Aβ deposition (amyloid positron emission tomography).DiscussionPeripheral immunity markers offer a non-invasive and cost-effective means of studying AD-related pathophysiological changes, providing valuable insights into its pathogenesis and treatment.HighlightsPeripheral immunity markers linked to cognitive decline and anxiety/depression.Low LMR, LYM, and high NLR linked to reduced CSF Aβ, impacting cognition.High PLR, NLR, SII associated with brain atrophy and hippocampal Aβ deposition.
| S-EPMC10730778 | biostudies-literature
Project description:Biological membranes are essential for cell viability. Their functional characteristics strongly depend on their protein content, which consists of transmembrane (integral) and peripherally associated membrane proteins. Both integral and peripheral inner membrane proteins mediate a plethora of biological processes. Whereas transmembrane proteins have characteristic hydrophobic stretches and can be predicted using bioinformatics approaches, peripheral inner membrane proteins are hydrophilic, exist in equilibria with soluble pools, and carry no discernible membrane targeting signals. We experimentally determined the cytoplasmic peripheral inner membrane proteome of the model organism Escherichia coli using a multidisciplinary approach. Initially, we extensively re-annotated the theoretical proteome regarding subcellular localization using literature searches, manual curation, and multi-combinatorial bioinformatics searches of the available databases. Next we used sequential biochemical fractionations coupled to direct identification of individual proteins and protein complexes using high resolution mass spectrometry. We determined that the proposed cytoplasmic peripheral inner membrane proteome occupies a previously unsuspected ?19% of the basic E. coli BL21(DE3) proteome, and the detected peripheral inner membrane proteome occupies ?25% of the estimated expressed proteome of this cell grown in LB medium to mid-log phase. This value might increase when fleeting interactions, not studied here, are taken into account. Several proteins previously regarded as exclusively cytoplasmic bind membranes avidly. Many of these proteins are organized in functional or/and structural oligomeric complexes that bind to the membrane with multiple interactions. Identified proteins cover the full spectrum of biological activities, and more than half of them are essential. Our data suggest that the cytoplasmic proteome displays remarkably dynamic and extensive communication with biological membrane surfaces that we are only beginning to decipher.
| S-EPMC3591654 | biostudies-literature
Project description:IntroductionPlatelets are the primary peripheral reserve of amyloid precursor protein (APP), providing more than 90% of blood amyloid-beta (Aβ). Some oxidative stress markers and neurotransmitter markers were also differentially expressed in the peripheral platelets of AD. Therefore, the present study explored the differences in platelet-associated biomarkers between AD and healthy controls using meta-analysis and systematic review to reveal the value of platelet in the pathogenesis and development of AD.MethodsWe searched all the related studies that probed into the platelets in AD based on PubMed, Embase, and web of science databases from the establishment to November 04, 2021.ResultsEighty-eight studies were included in the meta-analysis, and the platelets data of 702 AD and 710 controls were analyzed. The results of standardized mean difference (SMD) showed that platelets in AD had lower levels of APP ratio (SMD: -1.89; p < 0.05), ADAM10 (SMD: -1.16; p < 0.05), Na + -K + -ATPase (SMD: -7.23; p < 0.05), but higher levels of HMW/LMW tau (SMD: 0.92; p < 0.05), adenosine A2 receptor (SMD: 4.27; p < 0.05), MAO-B (SMD: 1.73; p < 0.05), NO (SMD: 4.25; p < 0.05) and ONOO- (SMD: 7.33; p < 0.05). In the systematic review, some other platelet markers seem to be meaningful in AD patients.ConclusionThe results of the present meta-analysis and systematic review demonstrated that the alterations of APP metabolic enzymes, oxidative stress markers, and neurotransmitter factors in platelets were similar to their changes in the central nervous system of AD, suggesting that platelet could be a good source of peripheral biomarkers and may play an important role in the pathophysiological development of AD.
| S-EPMC9921402 | biostudies-literature
Project description:Cervical mucus (CM) is a viscous fluid that is produced by the cervical glands and functions as a uterine cervix plug. Its viscosity decreases during ovulation, providing a window for non-invasive sampling. This study focuses on proteomic characterization of CM to evaluate its potential as a non-invasively acquired source of biomarkers and in understanding of molecular (patho)physiology of the female genital tract. The first objective of this work was to optimize experimental workflow for CM processing and the second was to assess differences in the proteomic composition of CM during natural ovulatory cycles obtained from intrauterine insemination (IUI) cycles and in vitro fertilization (IVF) cycles with controlled ovarian hyperstimulation. Proteomic analysis of CM samples revealed 4370 proteins involved in processes including neutrophil degranulation, cellular stress responses, and hemostasis. Differential expression analysis revealed 199 proteins enriched in IUI samples and 422 enriched in IVF. The proteins enriched in IUI were involved in phosphatidic acid synthesis, responses to external stimulus, and neutrophil degranulation, while those enriched in IVF samples were linked to neutrophil degranulation, formation of a cornified envelope and hemostasis. Subsequent analyses clarified the protein composition of the CM and how it is altered by hormonal stimulation of the uterus.
| S-EPMC9863546 | biostudies-literature
Project description:BACKGROUND Alzheimer's disease (AD) is the leading cause of dementia worldwide; however, the molecular mechanisms underlying its pathogenesis remain unclear. The present study aimed to discover some potential peripheral blood biomarkers for early detection of patients with AD. MATERIAL AND METHODS Publicly available AD datasets - GSE18309 and GSE97760 - were obtained from the Gene Expression Omnibus database, and limma package from Bioconductor was employed to search for differently expressed genes (DEGs). Weighted correlation network analysis was performed to identify DEGs with highly synergistic changes, and functional annotation of DEGs was performed using gene set enrichment analysis and Metascape. STRING and Cytoscape were used to construct protein-protein interaction networks and analyze the most significant hub genes. Thereafter, the Comparative Toxicogenomics Database (CTD) was used to identify hub genes associated with AD pathology, and Connectivity Map was used to screen small molecule drugs for AD. Finally, hub genes coupled with corresponding predicted miRNAs involved in AD were assessed via TargetScan, and functional annotation of predicted miRNAs was performed using DIANA database. RESULTS Our analyses revealed 5042 DEGs; based on functional analyses, these DEGs were mainly associated with oligosaccharide lipid intermediate biosynthetic process, cyclin binding, signaling pathways regulating pluripotency of ubiquitin mediated proteolysis, and extracellular matrix-receptor interaction. UBB, UBA52, SRC, MMP9, VWF, GP6, and PF4 were identified as the hub genes. The CTD showed that these hub genes are closely related with AD or cognition impairment. CONCLUSIONS The identified hub genes and corresponding miRNAs might be useful as potential peripheral blood biomarkers of AD.
| S-EPMC7453750 | biostudies-literature
Project description:Extracellular vesicles (EV) are involved in important processes of glioblastoma multiforme (GBM), including malignancy and invasion. EV secreted by glioblastoma cells may cross the hematoencephalic barrier and carry molecular cargo derived from the tumor into the peripheral circulation. Therefore, the determination of the molecular composition of exosomes released by glioblastoma cells seems to be a promising approach for the development of non-invasive methods of the detection of the specific exosomal protein markers in the peripheral blood. The present study aimed to determine the common exosomal proteins presented in preparations from different cell lines and search potential glioblastoma biomarkers in exosomes. We have performed proteomics analysis of exosomes obtained from the conditioned culture medium of five glioblastoma cell lines. A list of 133 proteins common for all these samples was generated. Based on the data obtained, virtual two-dimensional electrophoresis (2DE) maps of proteins presented in exosomes of glioblastoma cells were constructed and the gene ontology (GO) analysis of exosome proteins was performed. A correlation between overexpressed in glial cell proteins and their presence in exosomes have been found. Thus, the existence of many potential glioblastoma biomarkers in exosomes was confirmed.
| S-EPMC7399833 | biostudies-literature
Project description:Many factors are involved in Alzheimer's disease (AD) pathology including tau phosphorylation, amyloid β protein (Aβ) accumulation, lipid dysregulation, oxidative stress, and inflammation. The markers of these pathological processes in cerebral spinal fluid are used currently for AD diagnosis. However, peripheral biomarkers are the need of the hour for large population screening for AD. The main objective of the present study is to evaluate the peripheral levels of redox markers, lipid peroxidation (LPO) indicators, and pathological markers in AD patients. Blood was collected from AD patients (n = 45), controls (n = 45), and analyzed for pathological markers of AD including Aβ42 and tau, LPO, and redox indicators. Plasma Aβ42 was significantly (P < 0.001) elevated while total tau was decreased in AD compared to controls. Hydroxynonenal (HNE) and malondialdehyde (MDA) were higher (P < 0.001) in AD patients pointing the enhanced LPO in AD pathology. Receiver operating characteristic curve (ROC) analysis indicated that HNE is a better indicator of LPO compared to MDA. Plasma glutathione (GSH) level was significantly (P < 0.001) low while oxidized glutathione (GSSG) level was higher (P < 0.001) in AD patients with corresponding decrease in GSH/GSSG ratio (P < 0.001). ROC analysis indicated that GSH/GSSG ratio can be used as reliable indicator for redox imbalance in AD with a cutoff value of <8.73 (sensitivity 91.1%, specificity 97.8%). Correlation analysis revealed a positive correlation for both HNE and MDA with Aβ42 and a negative correlation with total tau. Negative correlation was observed between GSH/GSSG ratio and LPO markers. While oxidative stress has been implicated in pathology of various neurodegenerative disorders, the present study pinpoints the direct link between LPO and Aβ production in plasma of AD patients. Normally, at low amyloid concentration in body fluids, this peptide shown to function as a strong metal chelating antioxidant. However, when the Aβ production enhanced as in AD, through gain of functional transformation, Aβ evolves into prooxidant, thereby enhancing oxidative stress and LPO. Altered redox status with enhanced LPO observed in AD blood could contribute to the oxidation and S-glutathionylation proteins, which has to be addressed in future studies.
| S-EPMC5509803 | biostudies-other
Project description:BackgroundAlzheimer's disease (AD) is one of the major threats of the twenty-first century and lacks available therapy. Identification of novel molecular markers for diagnosis and treatment of AD is urgently demanded, and genetic biomarkers show potential prospects.MethodWe identify and intersected differentially expressed genes (DEGs) from five microarray datasets to detect consensus DEGs. Based on these DEGs, we conducted Gene Ontology (GO), performed the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, constructed a protein-protein interaction (PPI) network, and utilized Cytoscape to identify hub genes. The least absolute shrinkage and selection operator (LASSO) logistic regression was applied to identify potential diagnostic biomarkers. Gene set enrichment analysis (GSEA) was performed to investigate the biological functions of the key genes.ResultWe identified 608 consensus DEGs, several dysregulated pathways, and 18 hub genes. Sixteen hub genes dysregulated as AD progressed. The diagnostic model of 35 genes was constructed, which has a high area under the curve (AUC) value in both the validation dataset and combined dataset (AUC = 0.992 and AUC = 0.985, respectively). The model can also differentiate mild cognitive impairment and AD patients from controls in two blood datasets. Brain-derived neurotrophic factor (BDNF) and WW domain-containing transcription regulator protein 1 (WWTR1), which are associated with the Braak stage, Aβ 42 levels, and β-secretase activity, were identified as critical genes of AD.ConclusionOur study identified 16 hub genes correlated to the neuropathological stage and 35 potential biomarkers for the diagnosis of AD. WWTR1 were identified as candidate genes for future studies. This study deepens our understanding of the transcriptomic and functional features and provides new potential diagnostic biomarkers and therapeutic targets for AD.
| S-EPMC8236887 | biostudies-literature
Project description:Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. The AD pathophysiology entails chronic inflammation involving innate immune cells including microglia, astrocytes, and other peripheral blood cells. Inflammatory mediators such as cytokines and complements are also linked to AD pathogenesis. Despite increasing evidence supporting the association between abnormal inflammation and AD, no well-established inflammatory biomarkers are currently available for AD. Since many reports have shown that abnormal inflammation precedes the outbreak of the disease, non-invasive and readily available peripheral inflammatory biomarkers should be considered as possible biomarkers for early diagnosis of AD. In this minireview, we introduce the peripheral biomarker candidates related to abnormal inflammation in AD and discuss their possible molecular mechanisms. Furthermore, we also summarize the current state of inflammatory biomarker research in clinical practice and molecular diagnostics. We believe this review will provide new insights into biomarker candidates for the early diagnosis of AD with systemic relevance to inflammation during AD pathogenesis. [BMB Reports 2020; 53(1): 10-19].
| S-EPMC6999828 | biostudies-literature