Can newborn neurons reverse Alzheimer’s?

The ability to distinguish between similar memories depends on a small strip of brain tissue called the dentate gyrus. Studies on rats have shown that the dentate gyrus is one of the few parts of the brain that generates new neurons even in adulthood. It is thought that these new neurons help keep similar memories apart.

Whether something similar happens in humans is less clear. But a set of new results described this week at the Society for Neuroscience conference in Washington, DC, suggest that might be the case. And if it does, stimulating this process could lead to a new treatment for Alzheimer’s disease.

Until the 1960s, scientists believed that adult brains did not produce new neurons. Then evidence of young neurons began to emerge in the brains of adult rats and mice, particularly in the olfactory bulb, which processes smell, and in the dentate gyrus. These new neurons developed from neural progenitor cells, a type of undifferentiated neuron similar to stem cells, a process scientists call neurogenesis.

And it appears that, at least in mice, there is a link between these new neurons and Alzheimer’s disease. Genetically engineered mice with Alzheimer’s-like symptoms also had fewer young neurons in their brains. Two studies published in 2021 and 2022 showed that stimulating neurogenesis could improve memory in such animals. And a paper published in April this year found that boosting neurogenesis also causes other cells called microglia to begin clearing protein tangles, called amyloid-beta plaques, that characterize Alzheimer’s disease.

So far so promising—if you’re a mouse. But neurogenesis is difficult to study in humans. MRI scanners cannot see the growth of individual neurons. Scientists must take samples of brain tissue from cadavers and either stain them with chemicals that bind only young neurons, or measure genes expressed within brain cells to look for signs of youth.

Dozens of such letters have been published. But everyone who has found evidence of neurogenesis has failed to do so. The pro-neurogenesis camp believes that null results are due to poor quality brain tissue or unsophisticated preservation techniques. Opponents argue that either humans do not develop these neurons in the dentate gyrus, or if they do develop, there are too few of them to be useful.

Research presented in Washington strengthens the case for human neurogenesis. Maura Boldrini of Columbia University, María Llorens-Martín of the University of Madrid, Orly Lazarov of the University of Illinois at Chicago, and Hongjun Song of the University of Pennsylvania presented evidence of young neurons in the dentate gyrus of humans – although most of their findings have not yet been peer-reviewed. Has been.

Three of these researchers also studied the brains of healthy older people or people with Alzheimer’s disease. Their results suggested that the production of putative new neurons slows with age, and drops sharply in Alzheimer’s disease. Previous studies by the two groups also found that Alzheimer’s patients with more of these neurons had better memories.

But while the new research strengthens the case for human neurogenesis, it is not yet definitive. A group of researchers at Yale University questioned whether the staining technique used in one study was accidentally tagging other brain cells, such as astrocytes. They are also concerned that too few progenitor cells are found in the studies. One of the skeptics, John Arellano, asked, “Where are all the mothers of these baby neurons?”

There are more wrinkles. Dr. Song reportedly found a different set of genes expressed in young human neurons from those seen in other animal neurons. And some of the young neurons that both Dr. Song and Dr. Lazarov found in the brains of Alzheimer’s patients looked very different from similar neurons in healthy brains. If the new cells are defective in some way, increasing their numbers may not help.

Although not all scientists at the conference were convinced, some drugmakers seem to agree. In April, BioMed Industries, a California-based pharmaceutical firm, said early clinical trial results showed that a new drug the company claims increases neurogenesis in mice, improving memory in people with moderate Alzheimer’s. Has happened. If subsequent trials prove equally encouraging, it could be further evidence that there may indeed be something to the neurogenesis theory of Alzheimer’s.

© 2023, The Economist Newspaper Limited. All rights reserved. From The Economist, published under license. Original content can be found at www.economist.com

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Published: Jan 29, 2024, 06:00 PM IST