3D Super-Resolution Nanoscopes Used To Identify Amyloid Plaques

News   Jul 17, 2018 | Original story by Kayla Wiles at Purdue University Clearer and more detailed images reveal how amyloid plaques damage the brain, leading to Alzheimer's disease. Photo credit: Fenil Patel, Purdue University

One major problem with understanding Alzheimerâs disease is not being able to clearly see why the disease starts. A super-resolution "nanoscope" developed by Purdue University researchers now provides a 3D view of brain molecules with 10 times greater detail. This imaging technique could help reveal how the disease progresses and where new treatments could intervene.

The instrument helped Indiana University researchers better understand the structure of plaques that form in the brain of Alzheimerâs patients, pinpointing the characteristics that are possibly responsible for damage. Published findings appear in the journal Nature Methods.

Researchers at Purdue University demonstrate the technology behind the high-resolution images

"Brain tissue is particularly challenging for single molecule super-resolution imaging because it is highly packed with extracellular and intracellular constituents, which distort and scatter light â our source of molecular information," said Fang Huang, Purdue assistant professor of biomedical engineering. "You can image deep into the tissue, but the image is blurry."

The super-resolution nanoscopes, which Huang's research team has already developed to visualize cells, bacteria and viruses in fine detail, uses "adaptable optics" â deformable mirrors that change shape to compensate for light distortion, called "aberration," that happens when light signals from single molecules travel through different parts of cell or tissue structures at different speeds.

To tackle the challenge of brain tissue, Huangâs research team developed new techniques that adjust the mirrors in response to sample depths to compensate for aberration introduced by the tissue. At the same time, these techniques intentionally introduce extra aberration to maintain the position information carried by a single molecule.

The researchers used mice that were genetically engineered to develop the characteristic plaques that typify Alzheimerâs disease. Purdue researchers have taken 3D single molecule super-resolution images of the amyloid plaques associated with Alzheimer's disease in 30-micron thick sections of the mouse's frontal cortex. Image credit: Fenil Patel, Purdue University

Mlodzianoski, M. J., Cheng-Hathaway, P. J., Bemiller, S. M., Mccray, T. J., Liu, S., Miller, D. A., . . . Huang, F. (2018). Active PSF shaping and adaptive optics enable volumetric localization microscopy through brain sections. Nature Methods. doi:10.1038/s41592-018-0053-8 Monitoring Molecules Keeps Cells Healthy Obesity Linked to Increased Risk of Early-Onset Colorectal Cancer What Pneumococcus Says to Make You Sick

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