%0 Journal Article
%A Ballweg, Anna
%A Klaus, Carolin
%A Vogler, Letizia
%A Katzdobler, Sabrina
%A Wind, Karin
%A Zatcepin, Artem
%A Ziegler, Sibylle I
%A Secgin, Birkan
%A Eckenweber, Florian
%A Bohr, Bernd
%A Bernhardt, Maximilian Alexander
%A Fietzek, Urban
%A Rauchmann, Boris-Stephan
%A Stoecklein, Sophia
%A Quach, Stefanie
%A Beyer, Leonie
%A Scheifele, Maximilian
%A Simmet, Marcel
%A Joseph, Emanuel
%A Lindner, Simon
%A Berg, Isabella
%A Koglin, Norman
%A Mueller, Andre
%A Stephens, Andrew W
%A Bartenstein, Peter
%A Tonn, Joerg C
%A Albert, Nathalie L
%A Kümpfel, Tania
%A Kerschensteiner, Martin
%A Perneczky, Robert
%A Levin, Johannes
%A Paeger, Lars
%A Herms, Jochen
%A Brendel, Matthias
%T [18F]F-DED PET imaging of reactive astrogliosis in neurodegenerative diseases: preclinical proof of concept and first-in-human data.
%J Journal of neuroinflammation
%V 20
%N 1
%@ 1742-2094
%C London
%I BioMed Central
%M DZNE-2023-00348
%P 68
%D 2023
%Z CC BY
%X 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.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.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
%K Humans
%K Mice
%K Animals
%K Infant
%K Gliosis: pathology
%K Neurodegenerative Diseases: metabolism
%K Oligodendroglioma: metabolism
%K Oligodendroglioma: pathology
%K Cross-Sectional Studies
%K Pilot Projects
%K Alzheimer Disease: pathology
%K Positron-Emission Tomography: methods
%K Amyloid beta-Peptides: metabolism
%K Brain: metabolism
%K Mice, Transgenic
%K Inflammation: metabolism
%K Monoamine Oxidase: metabolism
%K Receptors, GABA: metabolism
%K Astrocytes (Other)
%K Deprenyl (Other)
%K MAO-B (Other)
%K PET (Other)
%K Amyloid beta-Peptides (NLM Chemicals)
%K Monoamine Oxidase (NLM Chemicals)
%K TSPO protein, human (NLM Chemicals)
%K Receptors, GABA (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:36906584
%2 pmc:PMC10007845
%R 10.1186/s12974-023-02749-2
%U https://pub.dzne.de/record/256590