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@INPROCEEDINGS{Lalia:283108,
      author       = {Lalia, Manvir and Wagner, Stephan and Hummel, Selina and
                      Thevis, Justus and Prtvar, Danilo and Zatcepin, Artem and
                      Zenatti, Valerio and Bartos, Laura and Tahirovic, Sabina and
                      Brendel, Matthias and Gnörich, Johannes},
      title        = {{C}ell‐{T}ype {S}pecific {C}ontributions to {M}etabolic
                      {C}onnectivity in an {A}lzheimer's {D}isease {M}ouse
                      {M}odel},
      journal      = {Alzheimer's and dementia},
      volume       = {21},
      number       = {S1},
      issn         = {1552-5260},
      reportid     = {DZNE-2026-00004},
      pages        = {e105605},
      year         = {2025},
      abstract     = {Background:The integration of molecular imaging and
                      multivariate connectivity approaches has emerged as a novel
                      approach to gain insights into the underlying
                      pathophysiology in neurodegenerative diseases. Metabolic
                      connectivity, in particular, has already demonstrated
                      disease-related pattern changes in both human and mammalian
                      brains. However, the cellular sources of disconnected brain
                      regions have not been investigated in detail. This study
                      aimed to elucidate the driving cellular sources of metabolic
                      connectivity in an Alzheimer's disease (AD) mouse model and
                      wild-type mice (WT).Method:After intravenous injection of
                      45MBq F-18-FDG, a static PET/MRI was performed on APPNL-G-F
                      and age- and sex-matched WT controls to obtain maps of
                      regional FDG uptake and metabolic connectivity. To calculate
                      the inter-regional correlations for metabolic connectivity,
                      26 delineated brain regions were used, resulting in a 26 ×
                      26 matrix of Pearson's correlation coefficient pairs.
                      Subsequently, the brain was extracted and separated into
                      fore- and hindbrain to achieve region-specific isolation of
                      microglia, astrocytes, oligodendrocytes, and neurons. The
                      radioactivity of each cell fraction was measured to quantify
                      the cell-specific FDG-uptake (Figure 1D).Result:APPNL-G-F
                      mice demonstrated higher FDG uptake compared to WT, along
                      with a significantly increased metabolic connectivity
                      between fore- and hindbrain (Figure 1A-C). Among all cell
                      types, microglial exhibited the highest single-cell FDG
                      uptake, in both mouse models (Figure 1E). In APPNL-G-F mice,
                      microglia, astrocytes, and oligodendrocytes displayed
                      increased FDG uptake, while neurons exhibited reduced uptake
                      compared to WT. The correlation between forebrain and
                      hindbrain cellular FDG uptake was significant across all
                      cell types in the APPNL-G-F model (microglia r=0.89, p =
                      0.0006; astrocytes r=0.65, p = 0.042; oligodendrocytes
                      r=0.77, p = 0.025 and neurons r=0.51, p = 0.005). In
                      contrast, WT mice did not exhibit any significant
                      correlation in single-cell uptake between forebrain and
                      hindbrain. Notably, region-specific microglial FDG uptake
                      correlated significantly with respective FDG-PET signals in
                      APPNL-G-F mice (forebrain r=0.89, p = 0.007; hindbrain
                      r=0.8, p = 0.014), whereas no significant correlation was
                      observed for other cell types.Conclusion:These findings
                      suggest that microglia are the primary drivers of the
                      increased forebrain-hindbrain metabolic connectivity
                      observed in the AD mouse model. Further RNA expression
                      analyses could provide valuable insights into the molecular
                      mechanisms underlying microglial metabolic coupling in
                      neurodegeneration.},
      month         = {Jul},
      date          = {2025-07-27},
      organization  = {Alzheimer’s Association
                       International Conference, Toronto
                       (Canada), 27 Jul 2025 - 31 Jul 2025},
      cin          = {AG Haass / AG Tahirovic},
      ddc          = {610},
      cid          = {I:(DE-2719)1110007 / I:(DE-2719)1140003},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)1 / PUB:(DE-HGF)16},
      doi          = {10.1002/alz70855_105605},
      url          = {https://pub.dzne.de/record/283108},
}