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@ARTICLE{Franz:285014,
      author       = {Franz, Jonas and Reichmann, Jakob and Eckermann, Marina and
                      Würfel, Thea and Groh, Artur and Qadri, Syed Fatima and
                      Schulz, Katja and Mollenhauer, Brit and Stadelmann,
                      Christine and Salditt, Tim},
      title        = {3{D} imaging of neuronal inclusions and protein aggregates
                      in human neurodegeneration by multiscale x-ray
                      phase-contrast tomography.},
      journal      = {Brain pathology},
      volume       = {36},
      number       = {2},
      issn         = {1015-6305},
      address      = {Oxford},
      publisher    = {Wiley-Blackwell},
      reportid     = {DZNE-2026-00140},
      pages        = {e70044},
      year         = {2026},
      abstract     = {This study leverages x-ray phase-contrast tomography (XPCT)
                      for detailed analysis of neurodegenerative diseases,
                      focusing on the three-dimensional (3D) visualization and
                      quantification of neuropathological features within fixed
                      human postmortem tissue. XPCT with synchrotron radiation
                      offers micrometer and even sub-micron resolution, enabling
                      us to examine intra- and extraneuronal aggregates and
                      inclusions such as Lewy bodies (LBs), granulovacuolar
                      degeneration (GvD), Hirano bodies (HBs), neurofibrillary
                      tangles (NFTs), β-amyloid plaques, and vascular amyloid
                      deposits in three dimensions. In the reconstructions, we
                      identified the highest electron densities in Hirano and LBs,
                      while NFTs exhibited no significant increase in XPCT
                      contrast. Using cutting-edge high-resolution x-ray
                      synchrotron beamlines, we were now able to detect even
                      detect subcellular differences in electron densities found
                      in GvD. Small-scale inhomogeneities of the electron density
                      were also detected in LBs, potentially relating to
                      inclusions of organelles. Additionally, we reveal here a
                      peculiar 3D geometry of HBs and demonstrate the
                      co-occurrence with GvD in the same neuron. These findings
                      underscore the potential of XPCT as a powerful, label-free
                      tool for spatially resolved neuropathological
                      investigations, opening new avenues for the systematic 3D
                      characterization of inclusions and aggregates in
                      neurodegeneration.},
      keywords     = {Humans / Imaging, Three-Dimensional: methods /
                      Neurodegenerative Diseases: pathology / Neurodegenerative
                      Diseases: diagnostic imaging / Inclusion Bodies: pathology /
                      Aged / Neurons: pathology / Female / Male / Aged, 80 and
                      over / Protein Aggregates: physiology / Brain: pathology /
                      Brain: diagnostic imaging / Neurofibrillary Tangles:
                      pathology / Lewy Bodies: pathology / Lewy bodies (Other) /
                      neurodegeneration (Other) / neuroimaging (Other) / protein
                      aggregates (Other) / synchrotron radiation (Other) / x‐ray
                      phase‐contrast tomography (Other) / Protein Aggregates
                      (NLM Chemicals)},
      cin          = {AG Fischer},
      ddc          = {610},
      cid          = {I:(DE-2719)1410002},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41033666},
      pmc          = {pmc:PMC12861568},
      doi          = {10.1111/bpa.70044},
      url          = {https://pub.dzne.de/record/285014},
}