FEASIBILITY STUDY OF SYNCHROTRON-BASED MICROTOMOGRAPHY TO IDENTIFY α-SYNUCLEIN OLIGOMERS IN POSTMORTEM TISSUE

Rodgers, Griffin Fischer; Erskine, Daniel; McKieth, Ian; Taylor, John-Paul; Mueller, Bert; Biskis, Christos; Schulz, Georg; Kuo, Willy; Hieber, Simone; Urwyler, Prabitha (22 July 2018). FEASIBILITY STUDY OF SYNCHROTRON-BASED MICROTOMOGRAPHY TO IDENTIFY α-SYNUCLEIN OLIGOMERS IN POSTMORTEM TISSUE. Alzheimer's & dementia, 14(7, Suppl.), P310-P310. Elsevier 10.1016/j.jalz.2018.06.104

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Background Lewy body disease (LBD) is the second most common cause of neurodegenerative dementia after Alzheimer’s disease and presents a challenge to healthcare services in an ageing society because current therapeutic approaches do not halt the disease’s progress. It has been suggested that aggregation of the protein α-synuclein plays a critical role in LBD. One pathway for aggregation involves the creation of low molecular weight α-synuclein oligomers, which have been observed to induce cell death. Precise location of Lewy bodies and their precursors could allow researchers to better relate their presence to clinical symptoms as well as infer their physiological effects. While conventional light microscopy of histological slices can visualize Lewy bodies and larger protein aggregates, it provides only two-dimensional information and diffraction-limited resolution prevents visualization of the smaller (approximately 50 nanometer) protein bundles. For this reason, we propose hard X-ray micro- and nano-tomography modalities for complementary, non-destructive, three-dimensional visualization of brain tissues taking advantage of developments at synchrotron radiation facilities. Methods As a proof-of-concept, we imaged paraffin-embedded fusiform gyrus tissue (provided by Newcastle Brain Tissue Resource) from a DLB case at the European Synchrotron Radiation Facility (ESRF Grenoble, France provided beamtime at ID19 from proposal MD-1055) using single-distance inline phase-contrast X-ray tomography with pixel size of 1.6 micrometers. A H&E stained histology slice of the same sample was also taken. Results A correspondence between the micro computed tomography and histology datasets could be made by tracking the orientation of vessels in the specimen. The micro computed tomography demonstrated as shown in figure (left) sufficient contrast and resolution for identification of the lower cortical layer as well as visualization of cells in three-dimensional manner, with confirmation from the annotated histology slice. Conclusions The present work serves as a proof-of-concept for the complementary use of phase contrast X-ray tomography and histology in the investigation of neurodegenerative diseases down to the cellular level. These results open the door for further nanometer resolution studies. Opens large image Nearby slices from phase-contrast microcomputed tomography (μ-CT) (left) and H&E stained histology (right) of diseased human brain tissue. The modalities can be used in complement, with the non-destructive μ-CT directing cutting planes for histological sectioning and extending histology into the third dimension.

Item Type:

Conference or Workshop Item (Abstract)

Division/Institute:

10 Strategic Research Centers > ARTORG Center for Biomedical Engineering Research > ARTORG Center - Gerontechnology and Rehabilitation
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology

UniBE Contributor:

Urwyler-Harischandra, Prabitha

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1552-5279

Publisher:

Elsevier

Language:

English

Submitter:

Angela Amira Botros

Date Deposited:

31 Jan 2019 11:14

Last Modified:

23 Oct 2019 19:34

Publisher DOI:

10.1016/j.jalz.2018.06.104

BORIS DOI:

10.7892/boris.122727

URI:

https://boris.unibe.ch/id/eprint/122727

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