TY  - JOUR
AU  - Ballweg, Anna
AU  - Klaus, Carolin
AU  - Vogler, Letizia
AU  - Katzdobler, Sabrina
AU  - Wind, Karin
AU  - Zatcepin, Artem
AU  - Ziegler, Sibylle I
AU  - Secgin, Birkan
AU  - Eckenweber, Florian
AU  - Bohr, Bernd
AU  - Bernhardt, Maximilian Alexander
AU  - Fietzek, Urban
AU  - Rauchmann, Boris-Stephan
AU  - Stoecklein, Sophia
AU  - Quach, Stefanie
AU  - Beyer, Leonie
AU  - Scheifele, Maximilian
AU  - Simmet, Marcel
AU  - Joseph, Emanuel
AU  - Lindner, Simon
AU  - Berg, Isabella
AU  - Koglin, Norman
AU  - Mueller, Andre
AU  - Stephens, Andrew W
AU  - Bartenstein, Peter
AU  - Tonn, Joerg C
AU  - Albert, Nathalie L
AU  - Kümpfel, Tania
AU  - Kerschensteiner, Martin
AU  - Perneczky, Robert
AU  - Levin, Johannes
AU  - Paeger, Lars
AU  - Herms, Jochen
AU  - Brendel, Matthias
TI  - [18F]F-DED PET imaging of reactive astrogliosis in neurodegenerative diseases: preclinical proof of concept and first-in-human data.
JO  - Journal of neuroinflammation
VL  - 20
IS  - 1
SN  - 1742-2094
CY  - London
PB  - BioMed Central
M1  - DZNE-2023-00348
SP  - 68
PY  - 2023
N1  - CC BY
AB  - 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
KW  - Humans
KW  - Mice
KW  - Animals
KW  - Infant
KW  - Gliosis: pathology
KW  - Neurodegenerative Diseases: metabolism
KW  - Oligodendroglioma: metabolism
KW  - Oligodendroglioma: pathology
KW  - Cross-Sectional Studies
KW  - Pilot Projects
KW  - Alzheimer Disease: pathology
KW  - Positron-Emission Tomography: methods
KW  - Amyloid beta-Peptides: metabolism
KW  - Brain: metabolism
KW  - Mice, Transgenic
KW  - Inflammation: metabolism
KW  - Monoamine Oxidase: metabolism
KW  - Receptors, GABA: metabolism
KW  - Astrocytes (Other)
KW  - Deprenyl (Other)
KW  - MAO-B (Other)
KW  - PET (Other)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Monoamine Oxidase (NLM Chemicals)
KW  - TSPO protein, human (NLM Chemicals)
KW  - Receptors, GABA (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:36906584
C2  - pmc:PMC10007845
DO  - DOI:10.1186/s12974-023-02749-2
UR  - https://pub.dzne.de/record/256590
ER  -