Neuron discovery could explain why some people don't get Alzheimer's

Some brains seem to fight off Alzheimer's disease. Even when signs like plaques and tangles are present, some people stay mentally sharp as they get older. This ability, called cognitive resilience, is a big mystery in brain science.

Researchers at the Netherlands Institute for Neuroscience, led by Evgenia Salta, have found new clues. Their work suggests that resilience might not depend on how many brain cells someone has. Instead, it might depend on how a special type of cell, called an immature neuron, reacts to damage.

Immature Neurons in the Adult Brain

For many years, scientists have wondered if the adult human brain still has a good number of "immature" neurons. These young-looking cells are found in the hippocampus, a part of the brain important for memory.

In animals like rodents, these cells help with memory and can even protect against Alzheimer's disease. But it's been a big debate whether humans continue to make new brain cells as adults, and what those cells do if they exist.

A new study in Cell Stem Cell offers some answers. Researchers looked at samples from the hippocampus of healthy older people, Alzheimer's patients, and people who were resilient to dementia. They used a method called single-nucleus RNA sequencing. They found immature neurons in all groups.

These cells had a "youthful signature," showing signs of young functions. These functions seemed to fade or break down in people with Alzheimer's disease.

Evgenia Salta, one of the authors, noted that they found these immature neurons in all groups, even in people over 80 years old.

The hippocampus is often called the brain's memory center. It's one of the first areas affected by Alzheimer's. The fact that immature neurons are present even in adults suggests they aren't just leftover cells from development. They might actively help the brain function when it's under stress.

How Immature Neurons Protect the Brain

The team's experiments showed that these neurons were always there, but their gene activity changed with the disease. In people who were more resilient to dementia, these neurons kept many of their youthful traits. This suggests that staying "young" helped protect their brains from dementia. However, in Alzheimer's patients, these youthful characteristics were reduced, meaning a possible loss of this protection.

The biggest surprise was that resilient people didn't have more of these cells than Alzheimer's patients. The key difference was not the number of immature neurons, but how they behaved.

In resilient individuals, these cells don't just sit there. They activate survival programs that help them resist damage. They also reduce signals of inflammation and cell death. This means the solution isn't just about replacing lost neurons.

Instead, these immature cells might act like caretakers. They could nourish the surrounding tissue and keep the brain youthful, much like fertilizer helps a fragile garden.

This changes the focus of research. Instead of asking if adult brain cell growth stops, the main question is how these cells help the brain become resilient or lead to disease.

Future Therapies

These findings have major implications. Future treatments could aim to preserve or bring back the youthful traits in these cell types. This might help restore balance in the aging hippocampus. Such a strategy could open new ways to prevent cognitive decline or protect against Alzheimer's.

Salta stated, "Cognitive resilience is extremely exciting. 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."

Deep Dive & References Persistent immature neurons in the human hippocampus are associated with cognitive resilience to Alzheimer’s disease - Cell Stem Cell, 2024