Validation Study for Candidate AD miRNA Biomarkers in Human CSF
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PROVIDER: PRJNA876275 | ENA |
REPOSITORIES: ENA
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Project description:We used an independent cohort of patient CSF samples from living donors obtained from the Shiley-Marcos Alzheimer's Disease Research Center at the Univ of CA, San Diego to validate the expression of 36 candidate AD miRNA biomarkers. The miRNAs were quantified on custom Taqman Low Density miRNA Arrays from ThermoFisher Scientific; miRNA probes were consistent to those used in the UH2 discovery arrays.
2022-09-03 | GSE212623 | GEO
Project description:Identify candidate miRNA biomarkers for AD in CSF.
2022-09-03 | GSE212558 | GEO
Project description:TLDA miRNA Screen for Candidate AD Biomarkers in CSF from Living Donors
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Project description:HIGHTLIGHTS-Improved protocol for ISF collection using microdialysis and CSF sampling in mice.-Combined LC‒MS/MS proteomics ISF and CSF analyses for the validation and description of potential new AD biomarkers.-ISF proteomics analysis to track disease progression at the neuronal and glial levels.-Identification of new biomarker candidates for Alzheimer’s disease.ABSTRACTBackground: Mass spectrometry (MS)-based cerebrospinal fluid (CSF) proteomics is an important method for discovering biomarkers of neurodegenerative diseases. CSF serves as a reservoir for interstitial fluid (ISF), and extensive communication between the two fluid compartments helps to remove waste products from the brain.New method: We performed proteomic analyses of both CSF and ISF fluid compartments using intracerebral microdialysis to validate and detect novel biomarkers of Alzheimer's disease (AD) in APPtg and C57Bl/6J control mice.Results: We identified up to 625 proteins in ISF and 4,483 proteins in CSF samples. By comparing the biofluid profiles of APPtg and C57Bl/6J mice, we detected 37 and 108 significantly up- and downregulated candidates, respectively. In ISF, 7 highly regulated proteins, such as Gfap, Aldh1l1, Gstm1, and Txn, have already been implicated in AD progression, whereas in CSF, 9 out of 14 highly regulated proteins, such as Apba2, Syt12, Pgs1 and Vsnl1, have also been validated to be involved in AD pathogenesis. In addition, we also detected new interesting regulated proteins related to the control of synapses and neurotransmission (Kcna2, Cacng3, and Clcn6) whose roles as AD biomarkers should be further investigated.Comparison with existing methods: This newly established combined protocol provides better insight into the mutual communication between ISF and CSF as an analysis of tissue or CSF compartments alone.Conclusions: The use of multiple fluid compartments, ISF and CSF, for the detection of their biological communication enables better detection of new promising AD biomarkers.KEYWORDSAlzheimer’s disease, CSF, ISF, proteomics, biomarkers, microdialysis, mass spectrometry, protein identification, neurodegeneration, brain fluids, expression profilesDATA AVAILABILITYDOI: 10.17605/OSF.IO/VWQ58PUBLICATIONS using this dataset:1)Gorska et al. 2024, Journal of Neuroscience Methodshttps://doi.org/10.1016/j.jneumeth.2024.1102392) to come
2024-08-28 | PXD048864 | Pride
Project description:Cross-sectional and longitudinal Analysis of CSF from controls and cases with AD
2015-07-15 | MSV000079192 | MassIVE
Project description:s synapse degeneration is an early event in Alzheimer’s disease (AD) pathophysiology, a biofluid marker of synapse loss in living patients could be a surrogate marker of disease prognosis and therefore would be an excellent addition to the AD biomarker arsenal. With direct access to the brain interstitial fluid, the cerebrospinal fluid (CSF) is a potential source of synapse-derived proteins that could be potential biomarkers of underlying synapse degeneration. The aim of this study was to identify, verify and evaluate a set of synaptic proteins as surrogate CSF markers of underlying synapse loss in AD patients. In the Discovery Stage, we combined high-throughput shotgun proteomics of the CSF with an exhaustive search of the literature and public databases for proteomic studies of the CSF and synapse. A thorough characterization of the synaptic component of the CSF identified 210 synaptic proteins that are detectable in human CSF. We selected an initial panel of 22 candidate biomarkers for evaluation. In the Verification Stage, 12 proteins were discarded due to poor detection by targeted mass spectrometry (Selected Reaction Monitoring, SRM). We confirmed the expression of the remaining 10 proteins either directly at (Calsynytenin-1, GluR2, GluR4, Neurexins 2A and 3A, Neuroligin-2, Syntaxin-1B, Thy-1 and Vamp-2), or surrounding (Tenascin-R), the human synapse using Array Tomography microscopy and biochemical fractionation methods. We quantified the synaptic panel by SRM in CSF samples from 2 independent clinical cohorts of cognitively normal controls and all clinical stages of AD (n=140). A set of the panel proteins demonstrated a non-linear profile distinct to that of existing biomarkers whereby the CSF levels were decreased at the earliest preclinical stage of AD, reflecting reduced synaptic density in these asymptomatic individuals and elevated at later symptomatic stages when neurodegeneration is widespread. In conclusion, we have identified a set of novel synapse-specific proteins that could have clinical value for assessing disease progression in individuals at-risk for AD and potentially in other neurological disorders characterized by early synapse loss.
2019-01-09 | PXD010356 | Pride
Project description:Alzheimer's disease (AD) is the most prevalent form of dementia and the number of AD patients is expected to increase as human life expectancy improves. The deposition of β-amyloid protein (Aβ) in the extracellular matrix and neurofibrillary tangles intracellularly are pathologic hallmarks of AD in the brain. However, there are no reliable circulating biomarkers for accurate diagnosis of AD. In this study, we employed high-resolution mass spectrometry and tandem mass tags (TMT) to identify candidate biomarkers for Alzheimer’s disease. A subset of the identified candidates was validated using multiplexed targeted PRM-LC-MS/MS analysis in an independent cohort.
2019-01-10 | PXD008098 | Pride
Project description:The Discovery and Validation of AML Prognostic Biomarkers
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Project description:The Discovery and Validation of AML Prognostic Biomarkers
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Project description:Replication-deficient adenovirus (Ad) type 5 capsids induce potent host innate immune responses. One system pivotal in host innate immune defense is the complement system. Intriguingly, excessive or inappropriate complement activation can result in extreme tissue damage and systemic inflammatory responses similar to those noted immediately after high dose systemic Ad vector injections. To determine if the complement system has a significant role in intensifying Ad-associated acute toxicities, we compared complement deficient (C3-knockout (KO)) mice responses to those of wild type (WT) mice following systemic challenge with Ad vectors. We noted not only thrombocytopenia and rapid increases in plasma IL-6, IFN-γ, TNF-α, and IL-12 levels previously reported after high dose Ad injections into WT mice, but also induction of cytokines IL-2, IL-4, IL-5 and IL-10, G-CSF and GM-CSF, and chemokines KC (CXCL1) and MIP-1. This expanded innate response “profile” was significantly blunted in Ad injected C3-KO mice, with a near complete avoidance of thrombocytopenia. Further validation for complement’s critical role in perturbing these innate responses against Ad were noted after comparison of gene specific RNA transcription levels in C3-KO to WT mice livers. Finally, these disparities were not attributed to a diminished ability of the Ad vectors to transduce C3-KO mice hepatocytes. These results suggest that Ad capsid interaction with the mammalian complement system may exacerbate the toxicity of systemic Ad injections, and thus represents a future target for manipulation in efforts to improve the efficacy and safety profile of Ad mediated gene delivery. Keywords: adenovirus, complement system, time course, innate immune response, toxicity
2006-02-15 | GSE4128 | GEO