Journal Article

DZNE-2026-00140

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 3D imaging of neuronal inclusions and protein aggregates in human neurodegeneration by multiscale x-ray phase-contrast tomography.

Franz, J. ; Reichmann, J. ; Eckermann, M. ; Würfel, T. ; Groh, A. ; Qadri, S. F. ; Schulz, K. ; Mollenhauer, B.DZNE* ; Stadelmann, C. ; Salditt, T.

2026
Wiley-Blackwell Oxford

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Please use a persistent id in citations: doi:10.1111/bpa.70044

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.

Keyword(s): Humans (MeSH) ; Imaging, Three-Dimensional: methods (MeSH) ; Neurodegenerative Diseases: pathology (MeSH) ; Neurodegenerative Diseases: diagnostic imaging (MeSH) ; Inclusion Bodies: pathology (MeSH) ; Aged (MeSH) ; Neurons: pathology (MeSH) ; Female (MeSH) ; Male (MeSH) ; Aged, 80 and over (MeSH) ; Protein Aggregates: physiology (MeSH) ; Brain: pathology (MeSH) ; Brain: diagnostic imaging (MeSH) ; Neurofibrillary Tangles: pathology (MeSH) ; Lewy Bodies: pathology (MeSH) ; Lewy bodies ; neurodegeneration ; neuroimaging ; protein aggregates ; synchrotron radiation ; x‐ray phase‐contrast tomography ; Protein Aggregates

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Contributing Institute(s):

1. Epigenetics and Systems Medicine in Neurodegenerative Diseases (AG Fischer)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

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