TY  - JOUR
AU  - Franz, Jonas
AU  - Reichmann, Jakob
AU  - Eckermann, Marina
AU  - Würfel, Thea
AU  - Groh, Artur
AU  - Qadri, Syed Fatima
AU  - Schulz, Katja
AU  - Mollenhauer, Brit
AU  - Stadelmann, Christine
AU  - Salditt, Tim
TI  - 3D imaging of neuronal inclusions and protein aggregates in human neurodegeneration by multiscale x-ray phase-contrast tomography.
JO  - Brain pathology
VL  - 36
IS  - 2
SN  - 1015-6305
CY  - Oxford
PB  - Wiley-Blackwell
M1  - DZNE-2026-00140
SP  - e70044
PY  - 2026
AB  - 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.
KW  - Humans
KW  - Imaging, Three-Dimensional: methods
KW  - Neurodegenerative Diseases: pathology
KW  - Neurodegenerative Diseases: diagnostic imaging
KW  - Inclusion Bodies: pathology
KW  - Aged
KW  - Neurons: pathology
KW  - Female
KW  - Male
KW  - Aged, 80 and over
KW  - Protein Aggregates: physiology
KW  - Brain: pathology
KW  - Brain: diagnostic imaging
KW  - Neurofibrillary Tangles: pathology
KW  - Lewy Bodies: pathology
KW  - Lewy bodies (Other)
KW  - neurodegeneration (Other)
KW  - neuroimaging (Other)
KW  - protein aggregates (Other)
KW  - synchrotron radiation (Other)
KW  - x‐ray phase‐contrast tomography (Other)
KW  - Protein Aggregates (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41033666
C2  - pmc:PMC12861568
DO  - DOI:10.1111/bpa.70044
UR  - https://pub.dzne.de/record/285014
ER  -