Some people develop the brain changes associated with Alzheimer’s disease without ever developing dementia. New research from the Netherlands Institute for Neuroscience suggests that immature neurons may help explain this cognitive resilience. Rather than merely replacing damaged cells, these rare neurons may activate protective processes that help the brain withstand inflammation, injury and the effects of disease.
“About 30 percent of older adults who develop Alzheimer’s never experience symptoms,” says Evgenia Salta, senior author of the study. “We really don’t know why. It’s a big mystery and a very important mystery.”
Understanding this resilience could change how researchers approach Alzheimer’s disease. Instead of focusing only on why brain cells deteriorate, scientists may also look for ways to help vulnerable regions remain healthy and functional.
Can the aging brain be repaired?
One possible explanation for cognitive resilience is that some brains become better able to repair or defend themselves as Alzheimer’s disease progresses.
“Perhaps we can add new brain cells to networks that are degenerating,” Salta says.
This possibility involves adult neurogenesis, the generation of new nerve cells, or neurons, in the adult brain. Neurons transmit information throughout the nervous system, allowing people to think, learn, remember and respond to their surroundings.
Scientists have demonstrated adult neurogenesis in several animal species, but whether it continues in the adult human brain has been debated for decades. If the human brain can produce new neurons later in life, those cells could help maintain important connections when aging and disease damage existing networks. However, finding immature neurons does not necessarily prove that they formed recently.
To investigate the possibility, Salta and her colleagues analyzed donated human brain tissue obtained through the Netherlands Brain Bank, a research resource that collects and stores brain samples.
The researchers compared three groups: people without detectable brain lesions, people who developed Alzheimer’s disease, and people who had Alzheimer’s-related changes in their brains but remained cognitively resilient.
The team focused on a small region within the brain’s memory center, one of the few areas thought to be capable of producing new neurons.
“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 researchers also developed a new method for analyzing the data. This allowed them to identify cells more accurately without relying heavily on assumptions derived from animal studies.
Immature neurons found in people over 80
The search produced an unexpected result: immature neurons were present in all three groups, including the brains of older adults.
The cells resemble neurons that have not fully matured, suggesting that the aging brain may retain cellular characteristics associated with development and adaptability.
“Even though the average age was over 80 years, we still found these immature neurons in all groups,” Salta says.
The most significant differences emerged when the researchers compared people who developed dementia with those who remained mentally alert despite having Alzheimer’s-related brain changes.
At first, the scientists expected resilient people to have larger numbers of relatively immature neurons. If these cells help replace damaged neurons, having more of them might explain why some brains withstand disease better than others.
Instead, the difference in cell numbers was much smaller than expected. This pointed to another possibility: the crucial difference may not be how many immature neurons are present, but how they respond when the brain is under attack.
Possible defenses against Alzheimer’s disease
When the researchers examined the activity of the immature neurons more closely, they found notable differences between the groups.
In cognitively resilient individuals, the cells showed signs of activating biological processes linked to survival and protection from damage.
“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.”
Inflammation is part of the body’s normal defense system, but persistent inflammation in the brain can cause damage and interfere with communication between neurons. Cell death gradually destroys the networks involved in memory and thinking.
The findings suggest that immature neurons in resilient brains may be better able to tolerate these harmful conditions. Their role may also extend beyond protecting themselves.
“It may be more than just replacing lost neurons,” Salta explains. “Perhaps these cells support surrounding tissues and help keep the brain functional and ‘youthful’. They may act as a kind of fertilizer for a garden that is starting to crumble.”
In this view, immature neurons might not only replace dying cells. They could also help maintain the environment around existing brain cells, allowing neural networks to keep functioning as Alzheimer’s-related damage accumulates.
Why the researchers are cautious
The results offer a possible explanation for cognitive resilience, but the researchers stress that they have not established exactly what these immature neurons do.
The proposed protective role is based on patterns observed in brain tissue, not on direct experiments demonstrating the cells’ function.
“We make inferences about cell function based on data, but this type of study cannot confirm that,” Salta explains.
This distinction is important because research on adult neurogenesis has attracted considerable public attention, sometimes leading to claims that go beyond what scientists have demonstrated.
The presence of immature neurons does not prove that new neurons are continuously generated in older people. It also does not prove that these cells prevent dementia.
Other biological mechanisms almost certainly contribute to cognitive resilience as well.
“This is one piece of a very large puzzle,” Salta concludes. “There is never just one factor that explains resilience.”
Could Alzheimer’s research reveal ways to protect the brain?
The findings raise broader questions about aging. Why do some people’s brains remain relatively stable while others experience progressive cognitive decline?
“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 the difference.”
The researchers plan to investigate how immature neurons communicate and interact with neighboring brain cells. These relationships could help determine whether the cells actively contribute to resilience and how their defensive responses work.
The study also reflects a broader shift in Alzheimer’s research. Traditionally, much of the field has focused on processes that damage the brain, including the accumulation of abnormal proteins and the loss of neurons. Researchers are increasingly asking why some brains continue to function despite those changes.
By identifying the mechanisms behind this natural resistance, scientists hope to find new ways to preserve memory and cognitive abilities as people age.
“Cognitive resilience is really interesting,” Salta says. “Understanding what it is that protects these brains could ultimately lead to new therapeutic strategies.”
Although a cure remains a long way off, the findings suggest that the aging human brain may possess protective capabilities that scientists are only beginning to understand.
Source: www.sciencedaily.com