For many years, scientists have focused on two harmful proteins, called A-beta and tau, when studying Alzheimer’s disease.
These proteins form sticky clumps in the brain known as amyloids. Amyloids damage brain cells and are easy to see under a microscope, so they became the main targets in Alzheimer’s research.
But a new study from Johns Hopkins University suggests there may be many more harmful proteins involved that don’t form clumps yet still hurt the brain.
The research team, led by Professor Stephen Fried, discovered more than 200 different misfolded proteins in older rats. These proteins could be linked to memory loss and other mental declines that come with age. Their findings were published on July 11 in the journal *Science Advances*.
Proteins are tiny machines that do many jobs inside our cells. To work properly, they must fold into the right shape. Sometimes, especially as we age, proteins fold incorrectly, or “misfold.”
When this happens, the proteins can stop working and even harm cells. In the past, scientists mostly worried about misfolded proteins that clump together to form amyloids, which are seen in Alzheimer’s and other brain diseases.
But Fried’s team found something new: many misfolded proteins that don’t form visible clumps still seem to cause trouble in the brain. “Amyloids are big and easy to spot, but our research shows they may be just the beginning,” Fried said. “We’re seeing hundreds of misfolded proteins that may be affecting brain health in other ways.”
To learn more, the researchers studied 17 rats that were two years old, which is old for a rat. All the rats came from the same colony and had similar life experiences. They tested the rats on memory and problem-solving tasks. Seven of the rats struggled with these tasks, while 10 performed just as well as much younger rats.
Then the scientists looked at the rats’ brains, focusing on a part called the hippocampus. This area helps with learning and remembering things. They studied more than 2,500 proteins in this brain region.
They found that over 200 proteins were misfolded only in the rats that had memory problems. These same proteins were fine in the rats with healthy brains.
This means that these misfolded proteins could be part of the reason some rats lost brain function while others didn’t. And it suggests that treatments should not focus only on A-beta and tau, but also on a much wider group of misfolded proteins.
Normally, cells have ways to spot and destroy misfolded proteins. But in this study, many harmful proteins escaped detection. It’s still unclear how they avoided being destroyed, but the researchers want to find out. Their next step is to look at these proteins under powerful microscopes to better understand their shapes and how they might be causing damage.
Fried says that this kind of research is personal for many people. “Almost everyone knows someone who has lost their memory or ability to think clearly as they’ve gotten older,” he said. “By learning what’s really happening in the brain, we can work toward better treatments and maybe even ways to prevent these diseases.”
In summary, this study opens the door to a new way of thinking about brain aging and memory loss. It shows that a large number of misfolded proteins—beyond just the usual suspects—may be damaging the brain.
Future treatments could aim at stopping these other proteins before they cause harm. It’s an important reminder that science is always uncovering new layers beneath the surface.
The study is published in Science Advances.
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