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Sci Adv. 2018 Nov 16;4(11):eaat7715. doi: 10.1126/sciadv.aat7715. eCollection 2018 Nov.

Label-free imaging of amyloid plaques in Alzheimer's disease with stimulated Raman scattering microscopy.

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State Key Laboratory of Surface Physics and Department of Physics, Multiscale Research Institute of Complex Systems, Human Phenome Institute, Key Laboratory of Micro and Nano Photonics Structures (Ministry of Education), Fudan University, Shanghai 200433, China.
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Alzheimer's Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Invenio Imaging Inc., Santa Clara, CA 95051, USA.


One of the key pathological features of Alzheimer's disease (AD) is the existence of extracellular deposition of amyloid plaques formed with misfolded amyloid-β (Aβ). The conformational change of proteins leads to enriched contents of β 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 (~10 cm-1) of amide I SRS spectra. Furthermore, SRS imaging of Aβ 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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