The elderly brain is less mature than you think and that could protect you from Alzheimer’s Disease

In an investigation to understand why some people remain resilient to Alzheimer’s Disease, Giorgia Tosoni and her colleagues from the Salta Lab discovered underdeveloped nerve cells in the elderly brain. These cells protect and stimulate the growth of surrounding cell types but turn inflammatory when Alzheimer’s disease sets in.

It is often believed that the adult brain is a rigid, slowly declining organ destined for Alzheimer’s Disease. But researchers at the Netherlands Institute for Neuroscience are getting closer to understanding just how outdated this idea is. Is it possible that the elderly brain is also able to generate new nerve cells after all?

In an effort to better understand the aging brain, Giorgia Tosoni dedicated her PhD to searching for underdeveloped nerve cells, otherwise known as immature neurons. Not only did she discover that they are indeed present, she also identified some key protective properties.

Alzheimer’s Resilience

Alzheimer’s Disease is defined by several symptoms including memory loss, behavioural changes, and problem solving difficulties. These symptoms are characterised by a build-up of specific proteins. When a brain is donated to the Netherlands Brain Bank, this build-up can be observed and the diagnosis confirmed. Occasionally, however, a donor is found to have had Alzheimer’s disease but with an important exception: they never had any symptoms. But how?

Tosoni believes Alzheimer’s resilience may have something to do with immature neurons in the brain’s memory hub, also known as the hippocampus. “In rodents, we know that the hippocampus is capable of generating new neurons. We also know that this process is impaired in the rodent model for Alzheimer’s Disease”, Tosoni explains. “In fact, if we boost the generation of new neurons, we can kind of rescue the cognitive symptoms of the rodent model of Alzheimer’s Disease.”

A century-old debate

Unfortunately, it’s not as simple in humans. Methodological limitations have made it impossible to confirm whether new neurons are also generated in the adult human brain. This has led to a debate among neuroscientists that has lasted a century and can evoke passionate discussions. Using the latest techniques in neuroscientific research, Tosoni was able to take an important step in this debate: identify whether the immature neurons are present in the adult hippocampus to begin with.

Tosoni investigated brain samples from donors without Alzheimer’s disease, donors resilient to Alzheimer’s disease, and donors with mild and severe Alzheimer’s disease. In all four groups, she identified immature neurons. “While this does not prove that the elderly brain still makes new neurons, it does prove that immature neurons persist in the elderly brain”.

That being said, she is keen to share a study that was published after she finished her PhD. “This wasn’t done by my lab, but it offers really compelling evidence that adult brain is able to generate new neurons”. Tosoni’s groupleader, Evgenia Salta, also commented on the paper in Science saying it “will make a huge contribution to the field”.

Immature and highly impressionable

When Tosoni looked at healthy and resilient brains, the immature neurons were widely connected. She pulls out four swirly diagrams, each one representing a different donor group. The immature neurons lie at the centre of each swirl, each line connecting it to another cell type. “These connections aren’t here for nothing. The immature neurons appear to have protective properties, supporting the other cells’ growth and survival.”

But the immature neurons also appear to be highly impressionable, as Tosoni found the opposite to be true in the Alzheimer’s sample. People with mild and severe Alzheimer’s had immature neurons that were much less connected to other cell types. In fact, these immature neurons were much more proinflammatory and diseased, meaning they were actually contributing to the problem.

Keep your neurons young

Tosoni cannot say with certainty during which stage the immature neurons shift to a more diseased state. But she can confirm that the health of these immature neurons play a role in either protecting the brain from developing the disease, or exacerbating the disease once it is set in motion.

To those actively trying to avoid Alzheimer’s Disease, Tosoni has a clear message: “Alzheimer’s is a complex disease. There’s probably not just one target that you can hit. That being said, having a healthy lifestyle and exercising both your brain and your body boosts several things at the same time. If your brain is fit, it is better able combat Alzheimer disease. Unfortunately there isn’t one cure, but doing exercise, eating a healthy diet, and keeping your inflammation low seems to be an effective first step.”

Giorgia Tosoni: New neurons, old questions | Cellular and molecular insights into the neurogenesis debate in Alzheimer’s disease. The defence took place on Thursday, June 19, 2025 in the Agnietenkapel, Oudezijds Voorburgwal 229-231, Amsterdam.