Elemental quantification and analysis of structural abnormalities in neurons from Parkinson's-diseased brains by X-ray fluorescence microscopy and diffraction

Karina Joppe; Jan-David Nicolas; Tilman A Grünewald; Marina Eckermann; Tim Salditt; Paul Lingor

doi:10.1364/BOE.389408

Elemental quantification and analysis of structural abnormalities in neurons from Parkinson's-diseased brains by X-ray fluorescence microscopy and diffraction

Biomed Opt Express. 2020 Jun 2;11(7):3423-3443. doi: 10.1364/BOE.389408. eCollection 2020 Jul 1.

Authors

Karina Joppe^{1

2

3}, Jan-David Nicolas^{4

3}, Tilman A Grünewald^{5

6}, Marina Eckermann⁴, Tim Salditt^{4

7}, Paul Lingor^{1

2

8

9}

Affiliations

¹ Department of Neurology, University Medical Center Goettingen, Robert-Koch-Straße 40, 37075 Goettingen, Germany.
² Center for Biostructural Imaging of Neurodegeneration, University Medical Center Goettingen, Von-Siebold-Straße 3a, 37075 Goettingen, Germany.
³ These authors contributed equally.
⁴ Institute for X-Ray Physics, Georg-August-University Goettingen, Friedrich-Hund-Platz 1, 37077 Goettingen, Germany.
⁵ European Synchrotron Radiation Facility, 71 Avenue des Martyrs, 38043 Grenoble, France.
⁶ CNRS, Centrale Marseille, Institut Fresnel, Aix-Marseille University, 52 Avenue Escadrille Normandie Niemen, 13013 Marseille, France.
⁷ Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Goettingen, Germany.
⁸ Department of Neurology, School of Medicine, University Hospital rechts der Isar, Technical University of Munich, Ismaninger Straße 22, 81675 Munich, Germany.
⁹ DFG Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), University Medical Center Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany.

Abstract

In this work we use scanning X-ray microscopy to study the structure and elemental composition of neuromelanin-positive neurons in substantia nigra tissue of Parkinson patients (PD) and controls. A total of 53 neurons were analyzed with X-ray fluorescence (XRF) and diffraction using sub-µm-focused synchrotron radiation. A statistical evaluation identified copper as the most group-discriminating element and indicated that interindividual and intraindividual variations are of great relevance in tissue measurements of diseased patients and prevent from automated group clustering. XRF analyses of two Lewy bodies (LBs) highlight a heterogeneity in elemental distributions in these LBs, whereas an innovative X-ray diffraction-based method approach was used to reveal β-sheet-rich crystalline structures in LBs. Overall, sub-µm-focus X-ray microscopy highlighted the elemental heterogeneity in PD pathology.