Immature Brain Cells May Hold a Clue to Why Some People Resist Alzheimer's Symptoms

Researchers at the Netherlands Institute for Neuroscience went looking for an extremely rare kind of cell in donated human brains, and they found it where they expected to: in a small region of the brain's memory center. The cells are called immature neurons. They turned up in people whose brains were healthy, in people who had developed Alzheimer's dementia, and in people whose brains showed Alzheimer's pathology but who had stayed mentally sharp. The average age of the donors was over 80.

The work centers on cognitive resilience, the ability of some people to keep their memory and thinking intact even when their brains show signs of disease. Evgenia Salta, the study's senior author, puts the scale of the puzzle this way: around 30 percent of older adults who develop Alzheimer's disease never experience its symptoms. "We really don't know why," she says, calling it a big and very important mystery.

One idea is that some brains can repair or shore up themselves as the disease advances. "Perhaps they can add new brain cells to a network that is degenerating," Salta says. That points to adult neurogenesis, the production of new neurons in an adult brain. Scientists have established that it occurs in several animal species, but whether it continues in adult humans has been debated for decades. Finding immature neurons does not by itself prove they were recently formed.

To test the question, the team used brain tissue from the Netherlands Brain Bank. They compared three groups: people with no detectable brain pathology, patients with Alzheimer's dementia, and people with Alzheimer's pathology who remained cognitively resilient. They focused on one small area of the memory center, considered one of the few places where new neurons might arise. Because the cells are so scarce, the group had to build new methods to locate them, zooming in on the precise spot where they were expected. They also developed new ways of analyzing the data that relied less on assumptions drawn from animal studies.

The researchers had expected resilient individuals to carry substantially more immature neurons, on the logic that more replacement cells might explain why some brains withstand the disease. That is not what they saw. The difference in numbers between the dementia group and the resilient group was much smaller than anticipated.

The difference showed up in how the cells behaved. In resilient individuals, the immature neurons appeared to switch on programs tied to survival and coping with damage, and they showed lower signals related to inflammation and cell death. Persistent inflammation in the brain can damage tissue and disrupt communication between neurons, and cell death gradually erodes the networks behind memory and thinking.

Salta suggests the cells' job may go beyond self-protection. "It might not be (only) about replacing lost neurons," she says. They could support the surrounding tissue and help keep the brain functional and "youthful," acting as a sort of fertilizer in a garden that has started falling apart.

She is careful about what the data can carry. The protective role is inferred from patterns in tissue, not demonstrated by experiments. "We assume the cells' function based on the data, but we cannot confirm it in this type of study," she says. The findings do not show that new neurons are continuously made in older humans, nor that these cells prevent dementia. Other mechanisms almost certainly contribute: "There will never be just one factor that explains resilience."

The next step is to study how immature neurons communicate with neighboring cells, which may show whether they actively contribute to resilience. Salta describes a decision point along the aging trajectory, where some people stay stable and others develop dementia, and says the aim is to understand what drives the difference. Any treatment built on this remains a distant prospect.