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001027717 0247_ $$2doi$$a10.1055/s-0043-1766342
001027717 037__ $$aFZJ-2024-04027
001027717 1001_ $$0P:(DE-Juel1)180330$$aEndepols, H.$$b0$$eCorresponding author$$ufzj
001027717 1112_ $$a61. Jahrestagung der Deutschen Gesellschaft für Nuklearmedizin$$cLeipzig$$d2023-04-19 - 2023-04-22$$wGermany
001027717 245__ $$aSV2A-PET in a tauopathy mouse model
001027717 260__ $$c2023
001027717 3367_ $$033$$2EndNote$$aConference Paper
001027717 3367_ $$2DataCite$$aOther
001027717 3367_ $$2BibTeX$$aINPROCEEDINGS
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001027717 3367_ $$2ORCID$$aLECTURE_SPEECH
001027717 3367_ $$0PUB:(DE-HGF)6$$2PUB:(DE-HGF)$$aConference Presentation$$bconf$$mconf$$s1719548193_9043$$xAfter Call
001027717 520__ $$aZiel/Aim Transgenic mouse models are frequently used to study the mechanismsof neurodegenerative diseases and possible therapeutic options. Weinvestigated the tauopathy mouse model TauRDΔK, which expresses the repeatdomain of human tau with deletion of the amino acid K280. TauRDΔK mice showa slow disease progression which makes them a suitable model for therapystudies. Unexpectedly, the PET tracer [18F]MNI-1126, which binds to the synapticvesicle protein SV2A, showed a significantly increased uptake in the brainof 16–18 months old TauRDΔK mice in the summed image analysis (n = 9; SUVRCer0.98 ± 0.03) compared to controls (n = 7; SUVRCer: 0.94 ± 0.02; p < 0.005).This is in contrast to studies with other tauopathy mouse models, which alldemonstrated reduced SV2A binding.Methodik/Methods To further investigate this surprising result, we performedkinetic modeling using the simplified reference tissue model in PMOD with thecerebellum as reference region as well as Western blot.Ergebnisse/Results The whole brain non-displaceable binding potential(BPnd) was significantly higher in TauRDΔK mice (0.24 ± 0.03) compared to controls(0.18 ± 0.06; p = 0.0276). This was confirmed by globally increased SV2A/actin ratio in Western blot (0.98 ± 0.24 in TauRDΔK mice versus 0.84 ± 0.11 incontrols). Voxel-wise comparison of BPnd revealed a wide-spead significantincrease of BPnd mirroring the elevated SUVRCer. Whole brain ratio of tracerdelivery R1 ( = K1/K1') was comparable in TauRDΔK mice (0.98 ± 0.04) and controls(0.94 ± 0.1; p = 0.2930). The efflux constant k2 was slightly lower inTauRDΔK mice (0.07 ± 0.02 1/ml) compared to controls (0.08 ± 0.03 1/ml), butnot statistically significant (p = 0.5432).Schlussfolgerungen/Conclusions Our results demonstrate that SV2A expressionwas globally increased in TauRDΔK mice. It is unlikely that this reflects synapticsprouting or a compensatory increase of synaptic vesicles, since a previousstudy has demonstrated a decline of synapsin expression as well as synapticdensity from 9 months of age. One possible explanation could be the increaseof mitochondrial SV2A expression, which will be evaluated in further studies.
001027717 536__ $$0G:(DE-HGF)POF4-5253$$a5253 - Neuroimaging (POF4-525)$$cPOF4-525$$fPOF IV$$x0
001027717 588__ $$aDataset connected to CrossRef Conference
001027717 7001_ $$0P:(DE-HGF)0$$aMandelkow, E. M.$$b1
001027717 7001_ $$0P:(DE-HGF)0$$aMandelkow, E.$$b2
001027717 7001_ $$0P:(DE-Juel1)156407$$aSchneider, Daniela$$b3$$ufzj
001027717 7001_ $$0P:(DE-Juel1)166419$$aNeumaier, B.$$b4$$ufzj
001027717 7001_ $$0P:(DE-Juel1)177611$$aDrzezga, A.$$b5$$ufzj
001027717 773__ $$a10.1055/s-0043-1766342
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001027717 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)156407$$aForschungszentrum Jülich$$b3$$kFZJ
001027717 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)166419$$aForschungszentrum Jülich$$b4$$kFZJ
001027717 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)177611$$aForschungszentrum Jülich$$b5$$kFZJ
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001027717 9141_ $$y2024
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001027717 9201_ $$0I:(DE-Juel1)INM-5-20090406$$kINM-5$$lNuklearchemie$$x0
001027717 9201_ $$0I:(DE-Juel1)INM-2-20090406$$kINM-2$$lMolekulare Organisation des Gehirns$$x1
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