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Self-perpetuating plaque formation in Alzheimer鈥檚

20 July 2016

Artist鈥檚 rendering of protein fibrils (in blue) and healthy proteins (in red) from computer simulations. Credit: Ivan Barun, dr. med." class="large-image" title="Artist鈥檚 rendering of protein fibrils (in blue) and healthy proteins (in red) from comp鈥

Using a combination of computer simulations and laboratory experiments, Dr Andela Saric (白小姐论坛 Institute for the Physics of Living Systems, Department of Physics & Astronomy) and colleagues were able to identify the necessary requirements for the self-replication of protein fibrils.

Replication of biological molecules, such as DNA, is the foundation of life, and it requires a number of helping molecules. However, protein fibrils, called amyloids, which are involved in neurodegenerative diseases such as Alzheimer鈥檚 disease, are able to replicate without any additional assistance. These fibrils, when intertwined and entangled with each other, form plaques found in the brains of Alzheimer鈥檚 patients.

Dr Saric's team found that the complicated process of the fibril self-replication is governed by a physical mechanism 鈥 a build-up of healthy proteins on the surface of existing fibrils. When this build-up reaches a certain amount it triggers fibril self-replication, at which point the rate at which听new protein听fibrils听are produced explodes, and results in rapid deterioration in brain function.

Formation of the first fibrils is very slow, and it typically takes several decades, which could explain why Alzheimer鈥檚 often affects people in their old age. But once the first fibrils are formed, they replicate and spread rapidly, making the disease unpredictable and difficult to control. Despite its importance, the fundamental mechanism of how protein fibrils can replicate without any additional help was not well understood.

The study suggests that by controlling how the healthy protein make contact with existing fibrils the spread of the plaques could be limited听and the disease contained. Dr Saric also argues that the findings could be of great interest in the field of nanotechnology, 鈥淥ne of the unfilled goals in nanotechnology is achieving efficient self-replication in manufacturing of nanomaterials. This is exactly what we鈥檝e observed happening with these fibrils 鈥 if we鈥檙e able to learn the design rules from this process, we may be able to achieve this goal.鈥

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