Scientists have found new clues about what may happen in the brain before Alzheimer’s disease develops.
The research suggests that problems with the way cells produce and use energy could appear before some of the better-known signs of the disease.
Alzheimer’s disease is the most common form of dementia. It slowly damages memory, thinking and the ability to carry out everyday activities, and the risk of developing it increases greatly with age.
For many years, scientists have focused heavily on a substance called amyloid-beta. In people with Alzheimer’s, this substance can build up between brain cells and form sticky clumps known as plaques.
These plaques are one of the main features doctors look for when studying Alzheimer’s disease. However, scientists still debate whether amyloid buildup is the original cause of the disease or one part of a much more complicated process.
Researchers from Yale-NUS College in Singapore investigated another possibility. They looked at whether problems with the way cells make and manage energy might begin before large amounts of amyloid appear.
Much of the energy needed by cells is produced inside tiny structures called mitochondria. They are often described as the cell’s power plants because they turn nutrients into energy that cells can use.
Mitochondria become less efficient as people grow older. Scientists have therefore become increasingly interested in whether these age-related changes could contribute to diseases such as Alzheimer’s.
In the study, researchers found signs that energy use inside cells was already changing before they detected a major buildup of amyloid-beta. This raises the possibility that problems with cell energy could be an early event in the development of the disease rather than simply a result of later brain damage.
The scientists conducted their experiments using tiny worms called Caenorhabditis elegans, or C. elegans. Although these worms are very different from humans, scientists often use them because many of the basic processes controlling cells, metabolism and aging are similar across different animals.
The researchers also tested metformin, a widely used medicine for type 2 diabetes. Metformin helps the body control blood sugar and has also attracted scientific interest because of its possible effects on metabolism and aging.
When the worms were given metformin, some of their energy-related problems improved. The treatment also helped the worms remain healthier and live longer.
The results suggest that improving the way cells handle energy could potentially influence some of the biological changes connected with Alzheimer’s. They also raise the possibility that treatment may be more effective if it targets very early changes, before serious damage to the brain has occurred.
However, the findings do not mean that metformin has been shown to prevent or treat Alzheimer’s disease in people. Worm experiments are an early stage of research, and treatments that produce promising results in laboratory animals do not always have the same effects in humans.
The research also supports a broader idea about Alzheimer’s disease. Instead of being caused by one abnormal substance alone, the disease may be closely connected with changes that happen throughout the body as we age.
If scientists can understand these early changes better, they may eventually find new ways to delay or prevent the damage that leads to memory and thinking problems. Research into metabolism could therefore provide another path for understanding a disease that has proved extremely difficult to treat.
The study was led by Jan Gruber and researchers at Yale-NUS College and was published in the scientific journal eLife.
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