
1.Medical Microspectroscopy, Department of Experimental Medical Science, Lund University, 22180, Lund, Sweden
2.Experimental Neuroinflammation Lab, Department of Experimental Medical Science, Lund University, 22180, Lund, Sweden
3.Experimental Dementia Research, Department of Experimental Medical Science, Lund University, 22180, Lund, Sweden
4.Synchrotron SOLEIL, L'Orme des Merisiers, 91192, Gif Sur Yvette Cedex, France
5.MAX IV Laboratory, 22100, Lund, Sweden
6.Lund Institute for advanced Neutron and X-ray Science (LINXS), 223 70, Lund, Sweden
Oxana Klementieva (oxana.klementieva@med.lu.se)
Published:31 August 2021,
Published Online:22 July 2021,
Received:23 December 2020,
Revised:20 June 2021,
Accepted:05 July 2021
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Gustavsson, N. et al. Correlative optical photothermal infrared and X-ray fluorescence for chemical imaging of trace elements and relevant molecular structures directly in neurons. Light: Science & Applications, 10, 1536-1545 (2021).
Gustavsson, N. et al. Correlative optical photothermal infrared and X-ray fluorescence for chemical imaging of trace elements and relevant molecular structures directly in neurons. Light: Science & Applications, 10, 1536-1545 (2021). DOI: 10.1038/s41377-021-00590-x.
Alzheimer's disease (AD) is the most common cause of dementia
costing about 1% of the global economy. Failures of clinical trials targeting amyloid-β protein (Aβ)
a key trigger of AD
have been explained by drug inefficiency regardless of the mechanisms of amyloid neurotoxicity
which are very difficult to address by available technologies. Here
we combine two imaging modalities that stand at opposite ends of the electromagnetic spectrum
and therefore
can be used as complementary tools to assess structural and chemical information directly in a single neuron. Combining label-free super-resolution microspectroscopy for sub-cellular imaging based on novel optical photothermal infrared (O-PTIR) and synchrotron-based X-ray fluorescence (S-XRF) nano-imaging techniques
we capture elemental distribution and fibrillary forms of amyloid-β proteins in the same neurons at an unprecedented resolution. Our results reveal that in primary AD-like neurons
iron clusters co-localize with elevated amyloid β-sheet structures and oxidized lipids. Overall
our O-PTIR/S-XRF results motivate using high-resolution multimodal microspectroscopic approaches to understand the role of molecular structures and trace elements within a single neuronal cell.
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