Some people have the brain changes associated with Alzheimer’s disease but never develop dementia. While others experience worsening memory and thinking problems, these people remain mentally alert despite signs of the disease in their brains. Scientists have long struggled to explain why.
Now, researchers at the Netherlands Institute of Neuroscience have discovered a promising clue. Their findings suggest that a rare group of brain cells, called immature neurons, may behave differently in people who are resistant to Alzheimer’s symptoms. Rather than simply replacing damaged cells, these neurons could help protect the brain from the harmful effects of disease.
This remarkable ability is known as cognitive resilience. It describes how some people retain their memory and thinking skills even when their brains show signs of damage or disease.
“About 30 percent of older people who develop Alzheimer’s disease never experience its symptoms,” says Evgenia Salta, lead author of the study. “We really don’t know why. It’s a big mystery and a very important mystery.”
Understanding this mystery could transform the way scientists approach Alzheimer’s disease, shifting their focus from what causes brain cells to deteriorate to what allows some brains to remain healthy and functional.
Can the aging brain repair itself?
One possible explanation for cognitive resilience is that some brains have a greater capacity to repair or protect themselves as Alzheimer’s disease progresses.
“Perhaps they could add new brain cells to a degenerating network,” Salta says.
This possibility involves a biological process called adult neurogenesis, which refers to the production of new nerve cells (neurons) in the adult brain. Neurons are specialized cells that transmit information throughout the nervous system, allowing us to think, learn, remember, and respond to our environment.
Scientists have established that adult neurogenesis occurs in several animal species. Whether this continues to occur in the adult human brain, however, has been the subject of scientific debate for decades.
If the human brain can produce new neurons later in life, these cells could help maintain important connections as aging and disease damage existing networks. However, the discovery of immature neurons does not necessarily prove that they were formed recently.
To investigate this possibility, Salta and colleagues examined human brain tissue obtained through the Dutch Brain Bank, a research resource that collects and preserves brain samples.
The researchers compared three groups: people without detectable brain pathology, patients who developed Alzheimer’s dementia, and individuals whose brains showed Alzheimer’s pathology but who remained cognitively resilient.
The team focused on a small region in the brain’s memory center, an area thought to be one of the few places where new neurons could grow.
Finding the relevant cells was far from simple.
“These cells are extremely rare, so we had to develop new ways to find them,” says Salta. “We really zoomed in on exactly where we expected them to be.”
Researchers have also developed new approaches to analyzing their data, allowing them to identify cells more precisely without relying heavily on assumptions drawn from animal studies.
Scientists discover immature neurons in brains over 80 years old
The research revealed something remarkable. Immature neurons were present in all three groups, including in the brains of older people.
These cells resemble neurons that are not yet fully mature, suggesting that the aging brain may retain cellular characteristics associated with development and adaptability.
“Even at an average age of over 80 years, we still found these immature neurons in all groups,” says Salta.
But the most intriguing discovery came when researchers compared the brains of people with dementia with those who had remained mentally sharp despite Alzheimer’s pathology.
Initially, scientists expected that resilient individuals would have many more immature neurons. If these cells help replace damaged neurons, their higher numbers could explain why some brains are resistant to the disease.
Instead, the difference in cell numbers was much smaller than expected.
This unexpected result pointed to another explanation. The important distinction may not be how many immature neurons a brain contains, but how those cells respond when the brain is attacked.
A hidden defense against Alzheimer’s damage
When the team took a closer look at the activity of immature neurons, they identified striking differences between the groups.
In cognitively resilient individuals, cells showed signs of activating biological processes associated with survival and protection from damage.
“In resilient individuals, these cells appear to activate programs that help them survive and cope with damage,” says Salta. “We also see weaker signals related to inflammation and cell death.”
Inflammation is part of the body’s normal defense system, but when it becomes persistent in the brain, it can contribute to damage and interfere with communication between neurons. Cell death, for its part, progressively disrupts the networks responsible for memory and thought.
The findings suggest that immature neurons in resilient brains may be better equipped to withstand these damaging conditions.
Even more surprising, their role could go beyond their own protection.
“It may not be (just) about replacing lost neurons,” says Salta. “It could be that these cells support surrounding tissues and help the brain stay functional and ‘young.’ They may act as a kind of fertilizer in a garden that has started to collapse.”
In other words, rather than serving only to replace dying neurons, immature cells could potentially help maintain the environment surrounding existing brain cells.
Such support could allow neural networks to continue functioning even as damage from Alzheimer’s disease accumulates.
Why scientists are cautious about this discovery
Although the findings offer a fascinating explanation for cognitive resilience, Salta points out that researchers haven’t established exactly what these immature neurons do.
Their conclusions about the cells’ possible protective roles are based on patterns observed in brain tissue and not on direct experiments demonstrating these functions.
“We assume how the cells work based on the data, but we can’t confirm it in this type of study,” she explains.
This distinction is particularly important because research on adult neurogenesis has attracted considerable public attention, sometimes leading to claims beyond what scientists have demonstrated.
The presence of immature neurons does not establish that new neurons are continually being produced in older humans, nor that these cells are responsible for preventing dementia.
Other biological mechanisms also almost certainly contribute to cognitive resilience.
“This is a piece of a very large puzzle,” Salta concludes. “There will never be just one factor explaining resilience.”
Could research into Alzheimer’s disease move towards protecting the brain?
The findings raise a broader question about aging: Why do some people’s brains remain relatively stable while others experience gradual cognitive decline?
“Somewhere along this trajectory there is some sort of decision point,” Salta says. “Some people remain stable, others develop dementia. We want to understand the causes of this difference.”
To explore this question further, the researchers plan to study how immature neurons communicate and interact with neighboring brain cells. Understanding these relationships can reveal whether cells actively contribute to resilience and how their protective responses might work.
The research also reflects a growing shift in how scientists view Alzheimer’s disease.
Traditionally, much of the field has focused on understanding the processes that damage the brain, including the accumulation of abnormal proteins and loss of neurons. More and more researchers are also wondering why some brains remain functional despite these changes.
By identifying the mechanisms behind this natural resistance, scientists hope to discover new ways to preserve memory and cognitive abilities as people age.
“Cognitive resilience is extremely exciting,” says Salta. “If we understand what protects these brains, it could eventually lead to new therapeutic strategies.”
Although practical treatments remain a distant possibility, the discovery suggests that even in old age, the human brain may possess protective capabilities that scientists are only beginning to understand.
Gn Health
