Alzheimer’s disease is often thought of as a condition that appears later in life, when memory problems become clear.
But scientists are now learning that the disease may begin much earlier, even when people seem healthy.
A new study from the Gladstone Institutes has uncovered how a common gene linked to Alzheimer’s disease may start affecting the brain long before symptoms appear.
The findings were published in Nature Aging and offer new hope for early treatment.
The gene, known as APOE4, is the strongest genetic risk factor for Alzheimer’s disease. Many people carry this gene without knowing it. While not everyone with APOE4 will develop Alzheimer’s, the risk is much higher compared to those without it.
In this study, researchers used mice to explore how this gene affects the brain over time. They focused on the hippocampus, a part of the brain that is essential for learning and memory.
Even in young mice that showed no signs of memory problems, the scientists found clear differences in brain activity. The neurons in these mice were smaller and more easily excited. This means they were firing signals more often than normal.
This early overactivity may seem harmless at first, but the researchers found that it predicted future problems. Mice with higher levels of early brain activity performed worse on memory tests later in life.
To understand why this happens, the team looked at gene activity inside the brain cells. They found that APOE4 increases the level of a protein called Nell2. This protein plays a key role in making neurons smaller and more sensitive to stimulation.
The discovery of Nell2 is important because it helps explain how the gene leads to brain changes. It also provides a new target for possible treatments.
The researchers then tested whether reducing Nell2 could improve brain function. Using advanced tools, they lowered the amount of this protein in adult mice. The results were very encouraging. The neurons returned to a more normal size and became less overactive.
This suggests that the harmful effects of APOE4 may not be permanent and could be reversed, at least in part. It also means that treatments might still work even after early changes have started.
Another important finding was that the problem seems to come directly from neurons, rather than other types of brain cells. This changes how scientists think about the disease and where they should focus future research.
This study adds to growing evidence that Alzheimer’s disease develops slowly over time. Early changes in brain activity may be one of the first signs, even before memory is affected.
If you care about Alzheimer’s, please read studies about the likely cause of Alzheimer’s disease , and new non-drug treatment that could help prevent Alzheimer’s.
For more health information, please see recent studies about diet that may help prevent Alzheimer’s, and results showing some dementia cases could be prevented by changing these 12 things.
