The Experts below are selected from a list of 70185 Experts worldwide ranked by ideXlab platform
Michel Bottlaender - One of the best experts on this subject based on the ideXlab platform.
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In vivo PET imaging of Neuroinflammation in Alzheimer’s disease
Journal of Neural Transmission, 2017Co-Authors: Julien Lagarde, Marie Sarazin, Michel BottlaenderAbstract:Increasing evidence suggests that Neuroinflammation contributes to the pathophysiology of many neurodegenerative diseases, especially Alzheimer’s disease (AD). Molecular imaging by PET may be a useful tool to assess Neuroinflammation in vivo, thus helping to decipher the complex role of inflammatory processes in the pathophysiology of neurodegenerative diseases and providing a potential means of monitoring the effect of new therapeutic approaches. For this objective, the main target of PET studies is the 18 kDa translocator protein (TSPO), as it is overexpressed by activated microglia. In the present review, we describe the most widely used PET tracers targeting the TSPO, the methodological issues in tracer quantification and summarize the results obtained by TSPO PET imaging in AD, as well as in neurodegenerative disorders associated with AD, in psychiatric disorders and ageing. We also briefly describe alternative PET targets and imaging modalities to study Neuroinflammation. Lastly, we question the meaning of PET imaging data in the context of a highly complex and multifaceted role of Neuroinflammation in neurodegenerative diseases. This overview leads to the conclusion that PET imaging of Neuroinflammation is a promising way of deciphering the enigma of the pathophysiology of AD and of monitoring the effect of new therapies.
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In vivo PET imaging of Neuroinflammation in Alzheimer's disease.
Journal of neural transmission (Vienna Austria : 1996), 2017Co-Authors: Julien Lagarde, Marie Sarazin, Michel BottlaenderAbstract:Increasing evidence suggests that Neuroinflammation contributes to the pathophysiology of many neurodegenerative diseases, especially Alzheimer’s disease (AD). Molecular imaging by PET may be a useful tool to assess Neuroinflammation in vivo, thus helping to decipher the complex role of inflammatory processes in the pathophysiology of neurodegenerative diseases and providing a potential means of monitoring the effect of new therapeutic approaches. For this objective, the main target of PET studies is the 18 kDa translocator protein (TSPO), as it is overexpressed by activated microglia. In the present review, we describe the most widely used PET tracers targeting the TSPO, the methodological issues in tracer quantification and summarize the results obtained by TSPO PET imaging in AD, as well as in neurodegenerative disorders associated with AD, in psychiatric disorders and ageing. We also briefly describe alternative PET targets and imaging modalities to study Neuroinflammation. Lastly, we question the meaning of PET imaging data in the context of a highly complex and multifaceted role of Neuroinflammation in neurodegenerative diseases. This overview leads to the conclusion that PET imaging of Neuroinflammation is a promising way of deciphering the enigma of the pathophysiology of AD and of monitoring the effect of new therapies.
Nicolas Arlicot - One of the best experts on this subject based on the ideXlab platform.
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Assessment of Translocator Protein Density, as Marker of Neuroinflammation, in Major Depressive Disorder: A Pilot, Multicenter, Comparative, Controlled, Brain PET Study (INFLADEP Study)
Frontiers in Psychiatry, 2018Co-Authors: Antoine Yrondi, Bruno Aouizerate, Wissam El-hage, Fanny Moliere, Claire Thalamas, Nicolas Delcourt, Marie Sporer, Simon Taib, Laurent Schmitt, Nicolas ArlicotAbstract:Background: Major depressive disorder (MDD) is a serious public health problem with high lifetime prevalence (4.4-20%) in the general population. The monoamine hypothesis is the most widespread etiological theory of MDD. Also, recent scientific data has emphasized the importance of immuno-inflammatory pathways in the pathophysiology of MDD. The lack of data on the magnitude of brain Neuroinflammation in MDD is the main limitation of this inflammatory hypothesis. Our team has previously demonstrated the relevance of [18F] DPA-714 as a Neuroinflammation biomarker in humans. We formulated the following hypotheses for the current study: (i) Neuroinflammation in MDD can be measured by [18F] DPA-714; (ii) its levels are associated with clinical severity; (iii) it is accompanied by anatomical and functional alterations within the frontal-subcortical circuits; (iv) it is a marker of treatment resistance. Methods: Depressed patients will be recruited throughout 4 centers (Bordeaux, Montpellier, Tours, and Toulouse) of the French network from 13 expert centers for resistant depression. The patient population will be divided into 3 groups: (i) experimental group-patients with current MDD (n = 20), (ii) remitted depressed group-patients in remission but still being treated (n = 20); and, (iii) control group without any history of MDD (n = 20). The primary objective will be to compare PET data (i.e., distribution pattern of Neuroinflammation) between the currently depressed group and the control group. Secondary objectives will be to: (i) compare Neuroinflammation across groups (currently depressed group vs. remitted depressed group vs. control group); (ii) correlate Neuroinflammation with clinical severity across groups; (iii) correlate Neuroinflammation with MRI parameters for structural and functional integrity across groups; (iv) correlate Neuroinflammation and peripheral markers of inflammation across groups. Discussion: This study will assess the effects of antidepressants on Neuroinflammation as well as its role in the treatment response. It will contribute to clarify the putative relationships between Neuroinflammation quantified by brain neuroimaging techniques and peripheral markers of inflammation. Lastly, it is expected to open innovative and promising therapeutic perspectives based on anti-inflammatory strategies for the management of treatment-resistant forms of MDD commonly seen in clinical practice. Clinical trial registration (reference: NCT03314155): https://www.clinicaltrials.gov/ct2/show/NCT03314155?term=Neuroinflammation&cond=depression&cntry=FR&rank=1.
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Radiopharmaceuticals for PET imaging of Neuroinflammation
Médecine Nucléaire, 2016Co-Authors: Anne-claire Dupont, Denis Guilloteau, Michael Kassiou, Maria Joao Ribeiro, Johnny Vercouillie, Andrew Katsifis, Nicolas ArlicotAbstract:Abstract Recently, accumulating evidence has revealed that Neuroinflammation appears to be the cornerstone of many neurological diseases including stroke, multiple sclerosis, Alzheimer's disease or Parkinson's disease. Neuroinflammation causes neuronal damages by activation of numerous cells and molecular mediators in diseases involving the inflammatory process. In this article, we focus on noninvasive molecular imaging of radioligands that target inflammatory cells and molecules involved in Neuroinflammation. PET is in fact one of the most promising imaging techniques to visualize and quantify Neuroinflammation in vivo. We have also summarized the potential Neuroinflammation imaging targets and corresponding PET radioligands.
Sang Ryong Kim - One of the best experts on this subject based on the ideXlab platform.
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translocator protein 18 kda negatively regulates inflammation in microglia
Journal of Neuroimmune Pharmacology, 2014Co-Authors: Keunryung Bae, Hyunjung Shim, Deebika Balu, Sang Ryong KimAbstract:Translocator protein 18 kDa (TSPO) is a mitochondrial outer membrane protein. Although TSPO expression is up-regulated during Neuroinflammation, the role of TSPO and its signaling mechanisms in regulation of Neuroinflammation remains to be elucidated at the molecular level. Here we demonstrate that TSPO is a negative regulator of Neuroinflammation in microglia. Over-expression of TSPO decreased production of pro-inflammatory cytokines upon lipopolysaccharide treatment while TSPO knock-down had the opposite effect. Anti-inflammatory activity of TSPO is also supported by increased expression of alternatively activated M2 stage-related genes. These data suggest that up-regulation of TSPO level during Neuroinflammation may be an adaptive response mechanism. We also provide the evidence that the repressive activity of TSPO is at least partially mediated by the attenuation of NF-κB activation. Neurodegenerative diseases are characterized by loss of specific subsets of neurons at the particular anatomical regions of the central nervous system. Cause of neuronal death is still largely unknown, but it is becoming clear that Neuroinflammation plays a significant role in the pathophysiology of neurodegenerative diseases. Understanding the mechanisms underlying the inhibitory effects of TSPO on Neuroinflammation can contribute to the therapeutic design for neurodegenerative diseases.
Julien Lagarde - One of the best experts on this subject based on the ideXlab platform.
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In vivo PET imaging of Neuroinflammation in Alzheimer’s disease
Journal of Neural Transmission, 2017Co-Authors: Julien Lagarde, Marie Sarazin, Michel BottlaenderAbstract:Increasing evidence suggests that Neuroinflammation contributes to the pathophysiology of many neurodegenerative diseases, especially Alzheimer’s disease (AD). Molecular imaging by PET may be a useful tool to assess Neuroinflammation in vivo, thus helping to decipher the complex role of inflammatory processes in the pathophysiology of neurodegenerative diseases and providing a potential means of monitoring the effect of new therapeutic approaches. For this objective, the main target of PET studies is the 18 kDa translocator protein (TSPO), as it is overexpressed by activated microglia. In the present review, we describe the most widely used PET tracers targeting the TSPO, the methodological issues in tracer quantification and summarize the results obtained by TSPO PET imaging in AD, as well as in neurodegenerative disorders associated with AD, in psychiatric disorders and ageing. We also briefly describe alternative PET targets and imaging modalities to study Neuroinflammation. Lastly, we question the meaning of PET imaging data in the context of a highly complex and multifaceted role of Neuroinflammation in neurodegenerative diseases. This overview leads to the conclusion that PET imaging of Neuroinflammation is a promising way of deciphering the enigma of the pathophysiology of AD and of monitoring the effect of new therapies.
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In vivo PET imaging of Neuroinflammation in Alzheimer's disease.
Journal of neural transmission (Vienna Austria : 1996), 2017Co-Authors: Julien Lagarde, Marie Sarazin, Michel BottlaenderAbstract:Increasing evidence suggests that Neuroinflammation contributes to the pathophysiology of many neurodegenerative diseases, especially Alzheimer’s disease (AD). Molecular imaging by PET may be a useful tool to assess Neuroinflammation in vivo, thus helping to decipher the complex role of inflammatory processes in the pathophysiology of neurodegenerative diseases and providing a potential means of monitoring the effect of new therapeutic approaches. For this objective, the main target of PET studies is the 18 kDa translocator protein (TSPO), as it is overexpressed by activated microglia. In the present review, we describe the most widely used PET tracers targeting the TSPO, the methodological issues in tracer quantification and summarize the results obtained by TSPO PET imaging in AD, as well as in neurodegenerative disorders associated with AD, in psychiatric disorders and ageing. We also briefly describe alternative PET targets and imaging modalities to study Neuroinflammation. Lastly, we question the meaning of PET imaging data in the context of a highly complex and multifaceted role of Neuroinflammation in neurodegenerative diseases. This overview leads to the conclusion that PET imaging of Neuroinflammation is a promising way of deciphering the enigma of the pathophysiology of AD and of monitoring the effect of new therapies.
William Charles Kreisl - One of the best experts on this subject based on the ideXlab platform.
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Neuroinflammation in Neurodegenerative Disorders—a Review
Current Neurology and Neuroscience Reports, 2017Co-Authors: Martin Schain, William Charles KreislAbstract:The potential for positron emission tomography (PET) to detect Neuroinflammation in vivo has sparked a remarkable interest in various disciplines of neuroscience. Early PET radioligands, such as [^11C]PK( R )-11195 for the 18-kDa translocator protein (TSPO) and [^11C]L-deprenyl for monoamine oxidase B, have been used in studies designed to clarify the role of Neuroinflammation in a variety of psychiatric and neurological disorders. Recent years have witnessed the development of several second-generation PET radioligands for TSPO and radioligands to measure endogenous targets that are active in various stages of the inflammatory cascade, such as cyclooxygenase and arachidonic acid. Here, we discuss some of the biomarkers for Neuroinflammation that are available for quantification with PET, as well as recent findings from studies where Neuroinflammation has been assessed in neurodegenerative disorders. In addition, we highlight the challenges to accurate interpretation of PET studies of Neuroinflammation.
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Neuroinflammation in Neurodegenerative Disorders-a Review.
Current neurology and neuroscience reports, 2017Co-Authors: Martin Schain, William Charles KreislAbstract:The potential for positron emission tomography (PET) to detect Neuroinflammation in vivo has sparked a remarkable interest in various disciplines of neuroscience. Early PET radioligands, such as [11C]PK(R)-11195 for the 18-kDa translocator protein (TSPO) and [11C]L-deprenyl for monoamine oxidase B, have been used in studies designed to clarify the role of Neuroinflammation in a variety of psychiatric and neurological disorders. Recent years have witnessed the development of several second-generation PET radioligands for TSPO and radioligands to measure endogenous targets that are active in various stages of the inflammatory cascade, such as cyclooxygenase and arachidonic acid. Here, we discuss some of the biomarkers for Neuroinflammation that are available for quantification with PET, as well as recent findings from studies where Neuroinflammation has been assessed in neurodegenerative disorders. In addition, we highlight the challenges to accurate interpretation of PET studies of Neuroinflammation.