A new breakthrough in the fight against neurogenerative disease
CU Medicine has made a breakthrough in studying brain diseases.
Researchers from CU Medicine have created a groundbreaking technique for deeper 3D visualisation of brain tissue structures. The innovative method can now be used by laboratories around the world to accelerate advances in the diagnosis and treatment of neurological conditions such as Parkinson’s disease, Alzheimer’s disease and cerebral small vessel disease. The findings have been selected as the cover story by the latest issue of renowned peer-reviewed journal Nature Methods.
As the global population ages, neurodegenerative diseases are imposing an increasingly heavy burden on society. Studying human brain tissue can advance our understanding of the pathological processes that lead to the onset of such diseases, and thus help improve diagnosis and treatment. Our ability to accurately visualise the structures of biological tissue is crucial to this effort. However, available techniques for visualising brain structures have proved limited and costly until now.
Looking deeper into the brain’s structure
One common visualisation technique, known as immunostaining, uses antibodies to detect and ‘label’ certain biological molecules in tissues. While effective in many cases, this approach is limited when it comes to studying three-dimensional structures because antibodies cannot reach deep into the tissues. This is because antibodies are sensitive to both heat and chemicals called denaturants, which can destabilise the antibodies and make them lose their functions.
Now, however, a research team led by Dr. Hei-ming Lai and Dr. Ho Ko from the Margaret K.L. Cheung Research Centre for Management of Parkinsonism at CU Medicine has discovered a technique that can achieve nearly fourfold deeper penetration of human brain tissues using just one-third of the typical amount of antibodies. The team developed a new chemical technology that takes commercially available antibodies and makes them much more resistant to heat and denaturants.
The heat-stable antibodies, termed SPEARs (synergistically protected polyepoxide-crosslinked Fab-complexed antibody reagents), can be used to label biological molecules deep inside intact tissues by flexibly choosing different incubation temperatures and denaturing chemicals: a strategy known as ThICK (thermal immunohistochemistry with optimised kinetics) staining.
The groundbreaking technique allows deeper 3D visualisation of brain tissue structures.
A rapid, simple and highly scalable method
ThICK staining achieves whole-organ immunolabelling faster than other state-of-the-art methods, from requiring one to eight weeks for each round of antibody staining to a much shorter time of one to three days. This new method is compatible with a wide range of commercially available antibodies, and different classes of tissue preservation and clearing methods. It can therefore be readily implemented in most laboratories.
Dr. Ko remarked, ‘SPEARs are our new weapons. This new technique is especially applicable to the study of neurodegenerative diseases. We hope our work can accelerate the path towards new tools for disease diagnosis and treatment paradigms in the future.’
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