期刊
SCIENCE ADVANCES
卷 4, 期 11, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aat7715
关键词
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资金
- National Institute of Biomedical Imaging and Bioengineering [R01EB017254]
- NIH [EB000768, S10 RR025645]
- National Key R&D Program of China [2016YFC0102100]
- National Natural Science Foundation of China [81671725]
- Shanghai Municipal Science and Technology Major Project [2017SHZDZX01]
One of the key pathological features of Alzheimer's disease (AD) is the existence of extracellular deposition of amyloid plaques formed with misfolded amyloid-beta (A beta). The conformational change of proteins leads to enriched contents of beta sheets, resulting in remarkable changes of vibrational spectra, especially the spectral shifts of the amide I mode. Here, we applied stimulated Raman scattering (SRS) microscopy to image amyloid plaques in the brain tissue of an AD mouse model. We have demonstrated the capability of SRS microscopy as a rapid, label-free imaging modality to differentiate misfolded from normal proteins based on the blue shift (similar to 10 cm(-1) ) of amide I SRS spectra. Furthermore, SRS imaging of A beta plaques was verified by antibody staining of frozen thin sections and fluorescence imaging of fresh tissues. Our method may provide a new approach for studies of AD pathology, as well as other neurodegenerative diseases associated with protein misfolding.
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