When beta amyloids clump together, the temperature in individual cells rises, researchers have shown.
Alzheimer’s is a fairly elusive disease; Although it is estimated that 44 million people worldwide are affected by Alzheimer’s, the disease is still difficult to diagnose and there are still no effective treatments. This is also because scientists are unable to get a grip on the causes of Alzheimer’s. Studies have shown that beta amyloids and tau proteins play a key role; they clump together in the brain to form so-called ‘aggregates’. These aggregates cause brain cells to die and the brain to shrink, resulting in memory loss and personality changes. But what exactly causes beta-amyloids to clump together is still unclear.
New insights
A new study – published in the magazine Journal of the American Chemical Society – certainly does not have all the answers to the open questions about Alzheimer’s. But it does provide new insights into what happens in a brain affected by Alzheimer’s. For example, the researchers have demonstrated for the first time on living cells that a clumping of beta-amyloids leads to a temperature change within individual cells.
The experiment
The researchers added beta-amyloids to human cell lines while measuring the temperature in human cells using very small temperature sensors known as FTPs (Fluorescent Polymeric Thermometers) are called. As soon as the beta-amyloids started to form so-called fibrils – thread-like protein clumps – the researchers saw the temperature in the cells rise. “We believe that when there is an imbalance in cells, for example when the concentration of beta-amyloids is slightly too high and the beta-amyloids start to accumulate, the cellular temperature increases,” said study researcher Chyi Wei Chung. “Overheating a cell is like frying an egg,” says researcher Kaminski Schierle. “As the temperature rises, the proteins clump together and are no longer functional.”
Domino
The temperature change can be traced back to the fibrils, the researchers show. “When the fibrils elongate, they release energy in the form of heat,” explains Schierle. And that heat can sometimes have a domino effect. Because the heat that the clumping beta amyloids give off can cause other, healthy beta amyloids to clump together. And this creates even more aggregates that are harmful to the brain. “The clumping of beta-amyloids requires quite a bit of energy,” says Schierle. “But once the agglomeration gets underway, it accelerates and releases more heat, allowing even more aggregates to form.” Chung: “And once those aggregates are ‘finished’, they can leave the cell and be taken up by neighboring cells and infect healthy beta-amyloids in those cells.”
But perhaps we are not completely powerless and it is possible to stop that domino effect. The researchers show – again using human cell lines – that a substance that prevents the clumping of beta-amyloids can also cause the temperature in individual cells to drop. It cautiously suggests that the compound could be used to treat Alzheimer’s, but more research and clinical studies are needed to confirm that.
Measuring cellular temperature may come in handy in that future research into this, as well as other potential treatments for Alzheimer’s. Indeed, a rise in temperature can reveal that proteins are clumping together and similarly, a stable cellular temperature can reveal that a potential treatment method can successfully prevent such clumping. In addition, measurements of the temperature of cells may also be used in the future in diagnosing Alzheimer’s and other neurodegenerative disorders.
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