Immature brain cells in the memory center of the adult brain (the hippocampus) may provide protection against Alzheimer’s disease and other forms of dementia. Researchers from the Netherlands Brain Institute concluded this in a publication this week Cell Stem Cell. They discovered that such young, immature neurons are also present in the brains of older people, and that they may make the brain resistant to memory loss in many different ways.
When studying brain tissue under the microscope, the researchers noticed that some people did have protein deposits in their brains – an indication of the development of Alzheimer’s disease – but never developed memory loss. “A really exciting finding,” says lead researcher Evgenia Salta from Greece. “Apparently something in the brains of these people makes them resistant to cognitive decline.”
In Alzheimer’s disease and other forms of dementia, brain cells slowly die. In the case of Alzheimer’s, the presence of protein deposits in the brain is usually considered the predictor for developing memory loss. Most medications that have appeared on the market in recent years against this neurodegenerative disease specifically focus on clearing these so-called plaques, but have little effect on improving memory. There is also busy experimenting with blood tests that can detect the protein clumps, so that a diagnosis can be made earlier.
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“Research often focuses on the damage Alzheimer’s disease does to the brain, but there is another way to look at it, through the lens of regeneration, rather than degeneration,” says Salta. “The big question in the search for a possible treatment is whether the brain can repair itself in these types of situations, or whether it can compensate for the loss of dying brain cells by creating new cells.”
In neuroscience, there has been speculation for years about the existence of immature brain cells and their possible protective functions. Some studies did find them. Other large and thorough studies found nothing. According to Salta, this is partly due to the varying quality of brain preparations in different places around the world: brain tissue must be prepared as quickly as possible after death in order to extract meaningful information from it.
Genetic code of the cell
“The Dutch Brain Bank has the best preparations in the world,” she says, without wanting to brag. “It is a small country with a good infrastructure to properly store samples, even a few hours after death.” With these preparations and the use of new techniques to look inside individual cells, the research group has been able to make the presence of immature brain cells “very plausible”.
They used for that single cell rna sequencinga new technique that makes it possible to read the genetic recipe book of one individual brain cell. This genetic code provides information about the possible functions of the cell. This study cannot yet demonstrate what exactly immature brain cells do to combat memory loss. According to Salta, you have to do functional experiments with those cells, and that is not possible in the human brain. “But we do have suspicions.”
These cells may be able to encourage other brain cells to survive better when they have to thrive in an environment of harmful protein clumps. Immature brain cells may also have anti-inflammatory properties. Inflammation in the brain is known to play a major role in the development of Alzheimer’s disease. And it is suspected that immature brain cells can help other cells communicate with each other. They therefore have a protective function and prevent damage caused.
“As we now understand it, these cells are a kind of fertilizer in a garden with slowly withering flowers,” says Salta. “When the flowers start to droop, these cells send signals that stimulate the brain to survive, youth and regeneration.”
Adding new cells to the brain
In their preparations, the researchers saw that people who remain resilient to memory loss have more such young brain cells than people who do develop complaints. “But that does not seem to be the whole story. There may also be a difference in genetic activity: which commands these cells can issue, and to what extent.” Later, Salta wants to investigate why some people with protein accumulations in their brains experience cognitive decline, while others do not. “How is that determined at the cellular level?”
It is still far too early for a look ahead to future treatment, says Salta, although she believes this research opens up a new fundamental line of thought: further research into which functions of those immature brain cells are so decisive for a resilient brain. “Maybe we can somehow strengthen those functions with a drug.” But according to Salta, it is too simple to say: we inject those immature brain cells into the brains of vulnerable people. “The question is how safe it is to simply add new cells to a neural network of cells that has formed together over decades. Especially if we do that in older people, you have to be careful that something like this does not turn out to be carcinogenic, for example.”
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