The mystery of cognitive resilience
Some brains resist Alzheimer's, even when the disease is already present. Researchers at the Netherlands Institute for Neuroscience have found that this likely depends on how specific brain cells, known as immature neurons, respond to damage caused by the disease. These insights are helping scientists unravel the mystery of cognitive resilience in aging.
Why do some people experience memory loss and cognitive decline as Alzheimer's builds up in their brain, while others stay mentally sharp? This question lies at the heart of new research into "cognitive resilience", a phenomenon that is gaining attention in neuroscience.
"Around 30 percent of older adults who develop Alzheimer's disease never experience its symptoms", Evgenia Salta, last author begins. "We really don't know why. That's a big mystery, and a very important one."
If we understand what protects these brains, it could eventually lead to new therapeutic strategies.
Can the brain repair itself?
One possible explanation is that resilient brains are better at repairing themselves during Alzheimer's. "Perhaps they can add new brain cells to a network that is degenerating", Salta says.
This idea is linked to a process called adult neurogenesis, which refers to the birth of new brain cells (neurons) in the adult brain. It has been well-established in other animals, but its existence in humans has been debated for years.
To study this, Salta's team used human brain tissue from the Netherlands Brain Bank, which collects and stores donated brain samples for research. They included brains from control donors with no brain pathology, Alzheimer's patients, and individuals with Alzheimer's pathology who remained resilient to developing dementia.
Even at an average age of over 80, we still found these immature neurons in all groups
The team focused on a small part of the brain's memory centre, likely one of the few areas where these new brain cells could form. "These cells are extremely rare, so we had to develop new ways to find them," Salta says. "We really zoomed in on the exact spot where we expected them to be."
The team also used new data analysis methods to make sure they could identify these cells as accurately as possible, without relying too much on assumptions from research on animals.
Finding immature neurons
Salta's team found what they were looking for: so-called "immature" neurons. These cells resemble young, not fully developed neurons. "Even at an average age of over 80, we still found these immature neurons in all groups," Salta says.
But the biggest surprise came next. While the team had expected to find much more of these cells in the resilient group than in the Alzheimer's patients, the difference was not as big as expected.
It's not the number, it's the behaviour
Surprisingly, the team found that the key difference lies in how the immature neurons behave. "In resilient individuals, these cells seem to activate programs that help them survive and cope with damage," Salta says. "We also see lower signals related to inflammation and cell death."
This points to a more complex story than they thought. "It might not be (only) about replacing lost neurons," she explains. "It could be that these cells support the surrounding tissue and help the brain stay functional and 'youthful'. They may act as a sort of fertilizer in a garden that has started falling apart."
Salta is careful not to jump to any conclusions, especially in light of recent media hype surrounding the topic. While the data suggest how cells might function, this can't be tested directly yet. "We assume the cells' function based on the data, but we cannot confirm it in this type of study," she explains.
"This is one piece of a very large puzzle," she concludes. "There will never be just one factor that explains resilience."
Towards new perspectives on Alzheimer's
Ultimately, Salta's research points to a broader question: what determines how the brain ages? "Somewhere along this trajectory, there's a kind of decision point," Salta explains. "Some people remain stable, others develop dementia. We want to understand what drives that difference."
Future work will focus on how these immature neurons interact with other brain cells, and how this interaction might influence resilience.
Although the findings do not provide immediate answers on why some cells behave different in Alzheimer's patients and resilient individuals, they contribute to a growing shift in Alzheimer's research: from focusing solely on disease progress to understanding resilience to it.
"Cognitive resilience is extremely exciting," Salta says. "If we understand what protects these brains, it could eventually lead to new therapeutic strategies." For now, the message is clear: the aging brain may be more adaptable, and more complex, than we once thought.
Source: Cell Stem Cell
