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@INPROCEEDINGS{Endepols:1027717,
      author       = {Endepols, H. and Mandelkow, E. M. and Mandelkow, E. and
                      Schneider, Daniela and Neumaier, B. and Drzezga, A.},
      title        = {{SV}2{A}-{PET} in a tauopathy mouse model},
      reportid     = {FZJ-2024-04027},
      year         = {2023},
      abstract     = {Ziel/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.},
      month         = {Apr},
      date          = {2023-04-19},
      organization  = {61. Jahrestagung der Deutschen
                       Gesellschaft für Nuklearmedizin,
                       Leipzig (Germany), 19 Apr 2023 - 22 Apr
                       2023},
      subtyp        = {After Call},
      cin          = {INM-5 / INM-2},
      cid          = {I:(DE-Juel1)INM-5-20090406 / I:(DE-Juel1)INM-2-20090406},
      pnm          = {5253 - Neuroimaging (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5253},
      typ          = {PUB:(DE-HGF)6},
      doi          = {10.1055/s-0043-1766342},
      url          = {https://juser.fz-juelich.de/record/1027717},
}