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@ARTICLE{Franz:645065,
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 = {PUBDB-2026-00570},
pages = {e70044},
year = {2025},
note = {Funded by ErUM-Pro Holo-Tomography Project 05K22MG1
(Salditt)},
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.},
cin = {FS DOOR-User},
ddc = {610},
cid = {$I:(DE-H253)FS_DOOR-User-20241023$},
pnm = {6G3 - PETRA III (DESY) (POF4-6G3) / DFG project
G:(GEPRIS)390729940 - EXC 2067: Multiscale Bioimaging: Von
molekularen Maschinen zu Netzwerken erregbarer Zellen
(390729940) / SFB 1456 A03 - Dimensionalitätsreduktion und
Regression im Wasserstein-Raum für quantitative
3D-Histologie (A03) (456837373)},
pid = {G:(DE-HGF)POF4-6G3 / G:(GEPRIS)390729940 /
G:(GEPRIS)456837373},
experiment = {EXP:(DE-H253)P-P10-20150101},
typ = {PUB:(DE-HGF)16},
doi = {10.1111/bpa.70044},
url = {https://bib-pubdb1.desy.de/record/645065},
}