STED imaging of tau filaments in Alzheimer’s disease cortical grey matter
| Autor: | Aleš Benda, Renee Whan, Claire Goldsbury, Hayden Aitken, Danielle S. Davies |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Tau protein tau Proteins Brain tissue 03 medical and health sciences Imaging Three-Dimensional 0302 clinical medicine Optics Alzheimer Disease Structural Biology medicine Humans Gray Matter Staining and Labeling biology business.industry Chemistry Optical Imaging STED microscopy Neurofibrillary Tangles Human brain Cortical grey matter Photobleaching Autofluorescence 030104 developmental biology medicine.anatomical_structure Cerebral cortex biology.protein business Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Journal of Structural Biology. 195:345-352 |
| ISSN: | 1047-8477 |
| Popis: | Alzheimer’s disease (AD) involves the propagation of filaments of tau protein throughout the cerebral cortex. Imaging tau filaments and oligomers in human brain at high resolution would help contribute insight into the mechanism and progression of tauopathic diseases. STED microscopy is a nano-scale imaging technique and we aimed to test the abilities of this method for resolving tau structures within human brain. Using autopsied 50 μm AD brain sections, we demonstrate that STED microscopy can resolve immunolabelled tau filaments at 77 nm resolution. Ribbon-like tau filaments imaged by STED appeared smooth along their axis with limited axial undulations. STED also resolved 70–80 nm wide tau puncta. Of the fluorophores tested, STAR635p was optimal for STED imaging in this tissue. This was in part due to brain tissue autofluorescence within the lower wavelength ranges (488–590 nm). Further, the stability and minimal photobleaching of STAR635p allowed STED z-stacks of neurons packed with tau filaments (neurofibrillary tangles) to be collated. There was no loss of x-y image resolution of individual tau filaments through the 20 μm z-stack. This demonstrates that STED can contribute to nano-scale analysis and characterisation of pathologies within banked human autopsied brain tissue. Resolving tau structures at this level of resolution provides promising avenues for understanding mechanisms of pathology propagation in the different tauopathies as well as illuminating what contributes to disease heterogeneity. |
| Databáze: | OpenAIRE |
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