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

Abstract

This study leverages X-ray phase-contrast tomography (XPCT) for detailed analysis of neurodegenerative diseases like Alzheimer's and Parkinson's, focusing on the 3D visualization and quantification of neuropathological features within fixed human postmortem tissue. XPCT, utilizing synchrotron radiation, offers micrometer resolution, enabling the examination of intraneuronal aggregates-Lewy bodies, granulovacuolar degeneration, Hirano bodies, and neurofibrillary tangles-and extracellular amyloid plaques and cerebral amyloid angiopathy in the fixed human tissue. This approach surpasses aspects of traditional histology, integrating with neuropathology workflows for the identification and high-resolution study of these features. It facilitates correlative studies and quantitative electron density assessments, providing insights into the structural composition and distribution of neurodegenerative pathologies.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

The work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Project-ID 432680300 - SFB 1456/A03 Mathematics of Experiment and EXC 2067/1-390729940. We also acknowledge assistance in visualization with NVIDIA IndeX (NVIDIA Corporation, USA).

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committee of the University Medical Center Goettingen, headed by Prof. Dr. Juergen Brockmoeller gave ethical approval for this work. Positive decision dated 20.8.2020.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

Raw data were generated at ESRF and DESY. Raw data will be released and made public two years after the beamtime. All treated datasets are available from the corresponding author on request. Exemplary datasets that support the findings of this study will be openly available in GRO.data upon publication.

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