Label-free imaging of amyloid plaques in Alzheimer's disease with stimulated Raman scattering microscopy.
Minbiao JiMichal ArbelLili ZhangChristian W FreudigerSteven S HouDongdong LinXinju YangBrian J BacskaiX Sunney XiePublished in: Science advances (2018)
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.
Keyphrases
- label free
- fluorescence imaging
- high resolution
- mouse model
- density functional theory
- single molecule
- photodynamic therapy
- optical coherence tomography
- molecular dynamics simulations
- gene expression
- molecular dynamics
- high throughput
- deep learning
- magnetic resonance imaging
- computed tomography
- mass spectrometry
- magnetic resonance
- single cell
- blood brain barrier
- high speed
- light emitting