Some people remain mentally alert despite the biological changes in their brains associated with Alzheimer’s disease. New research from the Netherlands Institute for Neuroscience suggests the answer may lie in how a rare group of brain cells called immature neurons respond to injury. The findings provide new insights into cognitive resilience, the brain’s ability to continue functioning despite illness.
One of the biggest unanswered questions in Alzheimer’s disease research is why it affects people so differently. As Alzheimer’s disease progresses, many people develop memory loss and dementia, but others have little or no cognitive decline despite having the same underlying brain pathology.
“About 30 percent of older people who develop Alzheimer’s disease never experience the symptoms,” says lead author Evgenia Salta. “We really don’t know why. It’s a big mystery and a very important mystery.”
Understanding what protects these people could ultimately lead to scientists finding new ways to treat or prevent dementia.
“Understanding what it is that protects these brains could ultimately lead to new therapeutic strategies.”
Can the aging brain replace damaged cells?
One possibility is that resilient brains are better able to repair themselves.
“Perhaps we can add new brain cells to networks that are degenerating,” Salta says.
The idea focuses on adult neurogenesis, the process by which new neurons are generated in the adult brain. Although adult neurogenesis is well documented in many animal species, scientists have long debated the extent to which neurogenesis occurs in humans, if at all.
To investigate, Salta and his colleagues examined brain tissue donated from the Dutch Brain Bank. The samples included healthy people, people with Alzheimer’s disease, and people who did not develop dementia but showed Alzheimer’s disease in their brains.
The researchers focused on a small region within the brain’s memory center, one of the few places where new neurons may still be developing.
“These cells are so rare that we needed to develop new ways to find them,” Salta says. “We actually zoomed in on exactly where we expected them to be.”
The research team also applied newly developed analytical methods designed specifically for human tissue, reducing reliance on assumptions based on animal studies.
Rare immature neurons persist into old age
The researchers identified the cells they were looking for: so-called immature neurons. This is similar to young neurons that are not yet fully mature.
“Even though the average age was over 80 years, we still found these immature neurons in all groups,” Salta says.
The results confirmed that these abnormal cells continue to exist even in very old brains.
But what surprised the researchers was that resilient people did not have dramatically more immature neurons than people with Alzheimer’s disease.
Brain cell behavior may be more important than numbers
Rather, the most important difference appeared to be in how the cells behaved.
“In resilient people, these cells appear to activate programs that help them survive and cope with injury,” Salta says. “We also saw a reduction in signals associated with inflammation and cell death.”
The findings suggest that these immature neurons do more than simply replace cells lost during disease.
“It may be more than just replacing lost neurons,” Salta explains. “Perhaps these cells support surrounding tissue and help keep the brain functional and ‘youthful’. They may act as a kind of fertilizer for a garden that is starting to crumble.”
Still, Salta cautions that these ideas remain hypothetical. Because the study examined donated brain tissue, the researchers cannot directly observe how cells function in a living brain.
“We make inferences about cell function based on data, but this type of study cannot confirm that,” she explains.
She also emphasizes that there is unlikely to be a single explanation for Alzheimer’s resilience.
“This is one piece of a very large puzzle,” she concludes. “There is never just one factor that explains resilience.”
New directions in Alzheimer’s disease research
The study also highlights broader questions about aging itself.
“There’s a kind of decision point somewhere along this trajectory,” Salta explains. “Some people remain stable, while others develop dementia. We want to understand what causes that difference.”
Future research will investigate how immature neurons communicate with other brain cells and whether their interactions help maintain memory and cognitive function.
The study does not explain why these cells behave differently in resilient people and those who develop dementia, but it reflects a growing shift in Alzheimer’s disease research. Rather than focusing solely on how the disease damages the brain, scientists are increasingly asking why some brains are able to withstand that damage.
“Cognitive resilience is really interesting,” Salta says. “Understanding what it is that protects these brains could ultimately lead to new therapeutic strategies.”
So far, the findings add to the evidence that the aging brain is more adaptive and more complex than scientists once thought.
