3D imaging of protein aggregates in human neurodegeneration by multiscale X-ray phase-contrast tomography

This study leverages X-ray phase-contrast tomography for detailed analysis of neurodegenerative diseases focusing on the 3D visualization and quantification of neuropathological features within fixed human postmortem tissue. X-ray phase-contrast tomography with synchrotron radiation offers micrometer and even sub-micron resolution, enabling us to examine intra- and extraneuronal aggregates and inclusions such as Lewy bodies, granulovacuolar degeneration, Hirano bodies, neurofibrillary tangles, β-amyloid plaques and vascular amyloid deposits in three dimensions (3D). In the reconstructions, we identified the highest electron densities in Hirano bodies and Lewy bodies while neurofibrillary tangles exhibit only slight alterations in X-ray phase-contrast tomography contrast. Using cutting edge high-resolution X-ray synchrotron beamlines we are now able to even detect subcellular differences of electron densities found in granulovacuolar degeneration. Small scale inhomogeneities of the electron density are also detected in Lewy bodies potentially relating to inclusions of organelles. Additionally, we reveal a peculiar 3D geometry of Hirano bodies and demonstrate the co-occurence with granulovacuolar degeneration in the same neuron. Utilizing X-ray phase-contrast tomography in a complementary fashion to traditional technologies, a quantitative, systematic and disease-overarching understanding of inclusions and aggregates in neurodegeneration can be achieved.