Alzheimer’s disease has long been associated with the buildup of sticky brain plaques, known as amyloids, which can kill neurons and impact cognitive function. However, a new study suggests that these plaques may not be operating alone. Researchers at Johns Hopkins University have identified more than 200 types of misfolded proteins in rats that could be linked to age-related cognitive decline.
The study, published in Science Advances, reveals that these misfolded proteins can still cause problems even if they don’t clump together into amyloids. The researchers studied 17 two-year-old rats and found that seven performed poorly on memory and problem-solving tests, while 10 performed as well as six-month-old rats.
The study used advanced techniques to measure more than 2,500 types of protein in the hippocampus, a part of the brain associated with spatial learning and memory. For the first time, scientists were able to determine whether individual proteins were misshapen or folded incorrectly, allowing them to identify which proteins are contributing to cognitive decline.
The findings suggest that some of these misfolded proteins are escaping the cell’s natural surveillance system, which identifies and destroys misbehaving proteins. This raises new questions about how these proteins are able to cause problems without forming amyloids.
The researchers believe that understanding what’s physically going on in the brain could lead to better treatments and preventive measures for Alzheimer’s and other diseases that affect cognitive function. The study’s lead author, Stephen Fried, said: “Amyloids are just the tip of the iceberg. We think there are a lot of proteins that can be misfolded, not form amyloids, and still be problematic.”
Source: https://medicalxpress.com/news/2025-07-misfolded-proteins-previously-contribute-alzheimer.html