For many people, Alzheimer’s disease seems to appear suddenly, with memory loss and confusion becoming clear only later in life. However, new research suggests that the process may begin much earlier, long before any symptoms are noticed.
Scientists at the Gladstone Institutes have found new evidence that changes in the brain can start early in people who carry a gene called APOE4. This gene is the strongest known genetic risk factor for Alzheimer’s disease. About one in four people carry this gene, and it is found in most patients with Alzheimer’s.
The study, published in the journal Nature Aging, looked at how APOE4 affects brain cells over time. The researchers used mice to study this process in detail, because it allows them to observe changes in the brain at different stages of life.
In the brain, memory is closely linked to a region called the hippocampus. This area helps people learn and remember information. The researchers found that in young mice with the APOE4 gene, brain cells in this region were already behaving differently, even though the mice still had normal memory at that stage.
These brain cells, called neurons, were smaller than normal and more active than they should be. This increased activity is known as hyperactivity. While it might sound harmless, too much activity can actually damage the brain over time.
The researchers discovered that the more hyperactive the neurons were in early life, the worse the memory problems became later on. This suggests that these early changes are not just minor differences, but important warning signs of future decline.
To understand why this happens, the team looked closely at what was going on inside the brain cells. They found that the APOE4 gene increases the production of a protein called Nell2. This protein causes neurons to shrink and become overly active.
This was an important discovery because it showed a clear chain of events. The gene leads to more Nell2, which then changes the size and behavior of brain cells, which in turn affects memory over time.
The most exciting part of the study came when the researchers tried to reverse these changes. Using a method to reduce the amount of Nell2 in the brain, they found that the neurons returned to a more normal size and activity level. This worked even in adult mice, suggesting that the damage may not be permanent.
This finding offers hope that future treatments could target Nell2 to protect the brain, especially in people who carry the APOE4 gene. It also shows that there may be a window of time when treatment could still be effective, even after early changes have begun.
The study also challenged previous ideas about how APOE4 works. Scientists had long believed that the gene mainly affects support cells in the brain. However, this research shows that the key effects come directly from neurons themselves.
Overall, this study provides a clearer picture of how Alzheimer’s disease may develop. It shows that changes in brain activity can happen early and may predict future memory problems.
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Source: Gladstone Institutes.
