6 results on '"Zatcepin, A."'
Search Results
2. [18F]F-DED PET imaging of reactive astrogliosis in neurodegenerative diseases: preclinical proof of concept and first-in-human data
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Ballweg, Anna, primary, Klaus, Carolin, additional, Vogler, Letizia, additional, Katzdobler, Sabrina, additional, Wind, Karin, additional, Zatcepin, Artem, additional, Ziegler, Sibylle I., additional, Secgin, Birkan, additional, Eckenweber, Florian, additional, Bohr, Bernd, additional, Bernhardt, Alexander, additional, Fietzek, Urban, additional, Rauchmann, Boris-Stephan, additional, Stoecklein, Sophia, additional, Quach, Stefanie, additional, Beyer, Leonie, additional, Scheifele, Maximilian, additional, Simmet, Marcel, additional, Joseph, Emanuel, additional, Lindner, Simon, additional, Berg, Isabella, additional, Koglin, Norman, additional, Mueller, Andre, additional, Stephens, Andrew W., additional, Bartenstein, Peter, additional, Tonn, Joerg C., additional, Albert, Nathalie L., additional, Kümpfel, Tania, additional, Kerschensteiner, Martin, additional, Perneczky, Robert, additional, Levin, Johannes, additional, Paeger, Lars, additional, Herms, Jochen, additional, and Brendel, Matthias, additional
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- 2023
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3. Depletion and activation of microglia impact metabolic connectivity of the mouse brain
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Gnörich, Johannes, primary, Reifschneider, Anika, additional, Wind, Karin, additional, Zatcepin, Artem, additional, Kunte, Sebastian T., additional, Beumers, Philipp, additional, Bartos, Laura M., additional, Wiedemann, Thomas, additional, Grosch, Maximilian, additional, Xiang, Xianyuan, additional, Fard, Maryam K., additional, Ruch, Francois, additional, Werner, Georg, additional, Koehler, Mara, additional, Slemann, Luna, additional, Hummel, Selina, additional, Briel, Nils, additional, Blume, Tanja, additional, Shi, Yuan, additional, Biechele, Gloria, additional, Beyer, Leonie, additional, Eckenweber, Florian, additional, Scheifele, Maximilian, additional, Bartenstein, Peter, additional, Albert, Nathalie L., additional, Herms, Jochen, additional, Tahirovic, Sabina, additional, Haass, Christian, additional, Capell, Anja, additional, Ziegler, Sibylle, additional, and Brendel, Matthias, additional
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- 2023
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4. [18F]F-DED PET imaging of reactive astrogliosis in neurodegenerative diseases: preclinical proof of concept and first-in-human data
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Anna Ballweg, Carolin Klaus, Letizia Vogler, Sabrina Katzdobler, Karin Wind, Artem Zatcepin, Sibylle I. Ziegler, Birkan Secgin, Florian Eckenweber, Bernd Bohr, Alexander Bernhardt, Urban Fietzek, Boris-Stephan Rauchmann, Sophia Stoecklein, Stefanie Quach, Leonie Beyer, Maximilian Scheifele, Marcel Simmet, Emanuel Joseph, Simon Lindner, Isabella Berg, Norman Koglin, Andre Mueller, Andrew W. Stephens, Peter Bartenstein, Joerg C. Tonn, Nathalie L. Albert, Tania Kümpfel, Martin Kerschensteiner, Robert Perneczky, Johannes Levin, Lars Paeger, Jochen Herms, and Matthias Brendel
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TSPO protein, human ,Deprenyl ,Immunology ,metabolism [Amyloid beta-Peptides] ,Pilot Projects ,Mice, Transgenic ,metabolism [Neurodegenerative Diseases] ,MAO-B ,Mice ,pathology [Alzheimer Disease] ,Cellular and Molecular Neuroscience ,metabolism [Oligodendroglioma] ,Receptors, GABA ,Humans ,Animals ,ddc:610 ,metabolism [Monoamine Oxidase] ,Monoamine Oxidase ,metabolism [Inflammation] ,pathology [Oligodendroglioma] ,Amyloid beta-Peptides ,General Neuroscience ,methods [Positron-Emission Tomography] ,Infant ,pathology [Gliosis] ,metabolism [Receptors, GABA] ,Cross-Sectional Studies ,PET ,Neurology ,metabolism [Brain] ,Astrocytes - Abstract
Objectives Reactive gliosis is a common pathological hallmark of CNS pathology resulting from neurodegeneration and neuroinflammation. In this study we investigate the capability of a novel monoamine oxidase B (MAO-B) PET ligand to monitor reactive astrogliosis in a transgenic mouse model of Alzheimer`s disease (AD). Furthermore, we performed a pilot study in patients with a range of neurodegenerative and neuroinflammatory conditions. Methods A cross-sectional cohort of 24 transgenic (PS2APP) and 25 wild-type mice (age range: 4.3–21.0 months) underwent 60 min dynamic [18F]fluorodeprenyl-D2 ([18F]F-DED), static 18 kDa translocator protein (TSPO, [18F]GE-180) and β-amyloid ([18F]florbetaben) PET imaging. Quantification was performed via image derived input function (IDIF, cardiac input), simplified non-invasive reference tissue modelling (SRTM2, DVR) and late-phase standardized uptake value ratios (SUVr). Immunohistochemical (IHC) analyses of glial fibrillary acidic protein (GFAP) and MAO-B were performed to validate PET imaging by gold standard assessments. Patients belonging to the Alzheimer’s disease continuum (AD, n = 2), Parkinson’s disease (PD, n = 2), multiple system atrophy (MSA, n = 2), autoimmune encephalitis (n = 1), oligodendroglioma (n = 1) and one healthy control underwent 60 min dynamic [18F]F-DED PET and the data were analyzed using equivalent quantification strategies. Results We selected the cerebellum as a pseudo-reference region based on the immunohistochemical comparison of age-matched PS2APP and WT mice. Subsequent PET imaging revealed that PS2APP mice showed elevated hippocampal and thalamic [18F]F-DED DVR when compared to age-matched WT mice at 5 months (thalamus: + 4.3%; p = 0.048), 13 months (hippocampus: + 7.6%, p = 0.022) and 19 months (hippocampus: + 12.3%, p p 18F]F-DED DVR increases of PS2APP mice occurred earlier when compared to signal alterations in TSPO and β-amyloid PET and [18F]F-DED DVR correlated with quantitative immunohistochemistry (hippocampus: R = 0.720, p R = 0.727, p = 0.002). Preliminary experience in patients showed [18F]F-DED VT and SUVr patterns, matching the expected topology of reactive astrogliosis in neurodegenerative (MSA) and neuroinflammatory conditions, whereas the patient with oligodendroglioma and the healthy control indicated [18F]F-DED binding following the known physiological MAO-B expression in brain. Conclusions [18F]F-DED PET imaging is a promising approach to assess reactive astrogliosis in AD mouse models and patients with neurological diseases.
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- 2023
5. Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia
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Dan Xia, Steve Lianoglou, Thomas Sandmann, Meredith Calvert, Jung H. Suh, Elliot Thomsen, Jason Dugas, Michelle E. Pizzo, Sarah L. DeVos, Timothy K. Earr, Chia-Ching Lin, Sonnet Davis, Connie Ha, Amy Wing-Sze Leung, Hoang Nguyen, Roni Chau, Ernie Yulyaningsih, Isabel Lopez, Hilda Solanoy, Shababa T. Masoud, Chun-chi Liang, Karin Lin, Giuseppe Astarita, Nathalie Khoury, Joy Yu Zuchero, Robert G. Thorne, Kevin Shen, Stephanie Miller, Jorge J. Palop, Dylan Garceau, Michael Sasner, Jennifer D. Whitesell, Julie A. Harris, Selina Hummel, Johannes Gnörich, Karin Wind, Lea Kunze, Artem Zatcepin, Matthias Brendel, Michael Willem, Christian Haass, Daniel Barnett, Till S. Zimmer, Anna G. Orr, Kimberly Scearce-Levie, Joseph W. Lewcock, Gilbert Di Paolo, and Pascal E. Sanchez
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Neuritic plaques ,Aging ,Vascular amyloid ,genetics [Alzheimer Disease] ,Plaque, Amyloid ,Astrogliosis ,Neurodegenerative ,metabolism [Microglia] ,Alzheimer's Disease ,Transgenic ,GABA ,Amyloid beta-Protein Precursor ,Mice ,Receptors ,metabolism [Amyloid beta-Protein Precursor] ,2.1 Biological and endogenous factors ,Phagocytic microglia ,Aetiology ,Plaque ,metabolism [Amyloidosis] ,Brain ,Amyloidosis ,metabolism [Receptors, GABA] ,genetics [Amyloid beta-Protein Precursor] ,Neurological ,Microglia ,metabolism [Alzheimer Disease] ,Biotechnology ,Amyloid ,Clinical Sciences ,metabolism [Amyloid beta-Peptides] ,Mice, Transgenic ,Cellular and Molecular Neuroscience ,Receptors, GABA ,Alzheimer Disease ,ddc:570 ,Acquired Cognitive Impairment ,Genetics ,Animals ,pathology [Plaque, Amyloid] ,Neurodegeneration ,Molecular Biology ,Lipid dyshomeostasis ,Neurology & Neurosurgery ,Amyloid beta-Peptides ,Animal ,Neurosciences ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Brain Disorders ,Disease Models, Animal ,metabolism [Brain] ,Disease Models ,Dementia ,Neurology (clinical) - Abstract
Background Genetic mutations underlying familial Alzheimer’s disease (AD) were identified decades ago, but the field is still in search of transformative therapies for patients. While mouse models based on overexpression of mutated transgenes have yielded key insights in mechanisms of disease, those models are subject to artifacts, including random genetic integration of the transgene, ectopic expression and non-physiological protein levels. The genetic engineering of novel mouse models using knock-in approaches addresses some of those limitations. With mounting evidence of the role played by microglia in AD, high-dimensional approaches to phenotype microglia in those models are critical to refine our understanding of the immune response in the brain. Methods We engineered a novel App knock-in mouse model (AppSAA) using homologous recombination to introduce three disease-causing coding mutations (Swedish, Arctic and Austrian) to the mouse App gene. Amyloid-β pathology, neurodegeneration, glial responses, brain metabolism and behavioral phenotypes were characterized in heterozygous and homozygous AppSAA mice at different ages in brain and/ or biofluids. Wild type littermate mice were used as experimental controls. We used in situ imaging technologies to define the whole-brain distribution of amyloid plaques and compare it to other AD mouse models and human brain pathology. To further explore the microglial response to AD relevant pathology, we isolated microglia with fibrillar Aβ content from the brain and performed transcriptomics and metabolomics analyses and in vivo brain imaging to measure energy metabolism and microglial response. Finally, we also characterized the mice in various behavioral assays. Results Leveraging multi-omics approaches, we discovered profound alteration of diverse lipids and metabolites as well as an exacerbated disease-associated transcriptomic response in microglia with high intracellular Aβ content. The AppSAA knock-in mouse model recapitulates key pathological features of AD such as a progressive accumulation of parenchymal amyloid plaques and vascular amyloid deposits, altered astroglial and microglial responses and elevation of CSF markers of neurodegeneration. Those observations were associated with increased TSPO and FDG-PET brain signals and a hyperactivity phenotype as the animals aged. Discussion Our findings demonstrate that fibrillar Aβ in microglia is associated with lipid dyshomeostasis consistent with lysosomal dysfunction and foam cell phenotypes as well as profound immuno-metabolic perturbations, opening new avenues to further investigate metabolic pathways at play in microglia responding to AD-relevant pathogenesis. The in-depth characterization of pathological hallmarks of AD in this novel and open-access mouse model should serve as a resource for the scientific community to investigate disease-relevant biology.
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- 2022
6. Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia
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Xia, Dan, primary, Lianoglou, Steve, additional, Sandmann, Thomas, additional, Calvert, Meredith, additional, Suh, Jung H., additional, Thomsen, Elliot, additional, Dugas, Jason, additional, Pizzo, Michelle E., additional, DeVos, Sarah L., additional, Earr, Timothy K., additional, Lin, Chia-Ching, additional, Davis, Sonnet, additional, Ha, Connie, additional, Leung, Amy Wing-Sze, additional, Nguyen, Hoang, additional, Chau, Roni, additional, Yulyaningsih, Ernie, additional, Lopez, Isabel, additional, Solanoy, Hilda, additional, Masoud, Shababa T., additional, Liang, Chun-chi, additional, Lin, Karin, additional, Astarita, Giuseppe, additional, Khoury, Nathalie, additional, Zuchero, Joy Yu, additional, Thorne, Robert G., additional, Shen, Kevin, additional, Miller, Stephanie, additional, Palop, Jorge J., additional, Garceau, Dylan, additional, Sasner, Michael, additional, Whitesell, Jennifer D., additional, Harris, Julie A., additional, Hummel, Selina, additional, Gnörich, Johannes, additional, Wind, Karin, additional, Kunze, Lea, additional, Zatcepin, Artem, additional, Brendel, Matthias, additional, Willem, Michael, additional, Haass, Christian, additional, Barnett, Daniel, additional, Zimmer, Till S., additional, Orr, Anna G., additional, Scearce-Levie, Kimberly, additional, Lewcock, Joseph W., additional, Di Paolo, Gilbert, additional, and Sanchez, Pascal E., additional
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- 2022
- Full Text
- View/download PDF
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