Journal
NATURE METHODS
Volume 15, Issue 8, Pages 583-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41592-018-0053-8
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Funding
- DARPA [D16AP00093]
- NIH [R35 GM119785, R01 AG050597, R01 AG023012, RF1 AG051495, UL1TR001108]
- Indiana Clinical and Translational Sciences Institute
- National Center for Advancing Translational Sciences
- Alzheimer's Association
- Jane & Lee Seidman Fund
- National Institute on Aging [NRSA F30 AG055261]
- Case Western Reserve University [CWRU NDD T32 NS077888, CWRU MSTP T32 GM725039]
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Application of single-molecule switching nanoscopy (SMSN) beyond the coverslip surface poses substantial challenges due to sample-induced aberrations that distort and blur single-molecule emission patterns. We combined active shaping of point spread functions and efficient adaptive optics to enable robust 3D-SMSN imaging within tissues. This development allowed us to image through 30-mu m-thick brain sections to visualize and reconstruct the morphology and the nanoscale details of amyloid-beta filaments in a mouse model of Alzheimer's disease.
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