Journal
NATURE NEUROSCIENCE
Volume 18, Issue 10, Pages 1518-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.4107
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Funding
- Japan Ministry of Education, Culture, Sports, Science and Technology
- Human Frontier Science Program
- Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) from Japan Agency for Medical Research and development, AMED
- Grants-in-Aid for Scientific Research [26290019, 15K14333, 15H01430] Funding Source: KAKEN
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Optical clearing methods facilitate deep biological imaging by mitigating light scattering in situ. Multi-scale high-resolution imaging requires preservation of tissue integrity for accurate signal reconstruction. However, existing clearing reagents contain chemical components that could compromise tissue structure, preventing reproducible anatomical and fluorescence signal stability. We developed Sca /eS, a sorbitol-based optical clearing method that provides stable tissue preservation for immunochemical labeling and three-dimensional (3D) signal rendering. Sca /eS permitted optical reconstructions of aged and diseased brain in Alzheimer's disease models, including mapping of 3D networks of amyloid plaques, neurons and microglia, and multi-scale tracking of single plaques by successive fluorescence and electron microscopy. Human clinical samples from Alzheimer's disease patients analyzed via reversible optical re-sectioning illuminated plaque pathogenesis in the z axis. Comparative benchmarking of contemporary clearing agents showed superior signal and structure preservation by Sca /eS. These findings suggest that Sca /eS is a simple and reproducible method for accurate visualization of biological tissue.
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