A powerful laser imaging technique has been used by researchers to show how minute quantities of a protein associated with Alzheimer’s disease trigger a process which may be crucial to its onset and spread. The study, by researchers at the University of Cambridge and co-funded by Alzheimer’s Research UK, is reported in The Journal of Biological Chemistry.
The research focused on tau, a protein normally found inside healthy brain cells. In Alzheimer’s, tau malfunctions and clumps into ‘tau tangles’, which appear to play a critical role in preventing their brain cells from working properly.
In the new study, researchers investigated how this happens by adding tiny quantities of normal tau to the outside of brain cells. To their surprise, the cells immediately started to take up the protein, which triggered the characteristic clumping of tau seen in Alzheimer’s. These clumps could then be seen to trigger a chain reaction, causing “healthy tau” inside cells to misbehave and also clump together.
Although seen in model cell cultures, the observations may show how the events that cause Alzheimer’s begin.
“These are molecular-level glimpses of what may be going on,” Clemens Kaminski, Professor of Chemical Physics at the University of Cambridge, who led the research, said. “We are just beginning to see the molecular steps that may provide an explanation for what we see in the brains of patients who have died of Alzheimer’s.”
There are a number of processes that could trigger tau to be release from nerve cells, with head injury one possible cause, but the researchers involved are urging caution about the results. They stress that the study used a model cell culture and that the processes, which enable the disease to take root and develop in the brain, could be far more complicated.
“The study underlines how significant the uptake of small quantities of tau might be as an initiator for the conditions that then prevail in the brains of people with Alzheimer’s”, Kaminski added. “It is one piece in the puzzle that could provide us with an explanation as to why head injuries may be connected to the disease. It’s not necessarily correct – but it is plausible.”
The Cambridge Laser Analytics Group, to which Kaminski and his colleagues belong, is a team of physicists, biologists, chemists and engineers who, over many years, have developed laser-based imaging techniques to study the molecular mechanisms behind diseases like Alzheimer’s. The team’s future research will focus on identifying how and where tau enters nerve cells, what happens when it meets tau already present in the cell and how clumps of the protein may move between cells.
Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, said:
“The state-of-the-art technology used by this research team allows a unique insight into the molecular events that occur in Alzheimer’s. Investigating how the tau protein spreads between nerve cells can help researchers better understand what causes the disease and offer new approaches for treatments. It is unclear from this study whether head injury could trigger this molecular process, but it is a risk factor for dementia that needs to be investigated further.”
Read our blog on a recent visit to Prof Kaminski’s research lab.
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