Scientists at Northwestern University, USA, for the first time transformed human stem embryonic cells into an important type of neuron, whose early death in Alzheimer's disease is the main cause of memory loss.

A new possibility of reprogramming stem cells and growing an unlimited number of human neurons will give scientists the opportunity to quickly test drugs for the treatment of this neurodegenerative disease, will allow to study why neurons die and will help develop methods for transplanting new neurons to patients with Alzheimer's disease.

The article about the research was published in the journal Stem Cells.

These vital neurons, called basal cholinergic neurons of the forebrain, help the hippocampus retrieve from the brain memories. The population of such neurons in the brain is relatively small, and their loss has a quick and destructive effect on the ability to memorize.

"Now that we know how to get these cells, we can study them in the tissue culture and find out what can be done to prevent their death," says senior study author Dr. Jack Kessler, professor of neurology and Stem cell biology of the Feinberg School of Medicine of Northwestern University.

The lead author of the article is Christopher Bissonnette, a former doctoral neurologist who worked for six years in the laboratory of Professor Kessler, trying to "crack" the genetic code of stem cells and get neurons.

"This method of obtaining neurons allows growing an almost infinite number of such cells in the laboratory, which will give other scientists an opportunity to study why this cell population is selectively killed in Alzheimer's disease," Bissonnett.

The possibility of obtaining such cells means that researchers can quickly test thousands of different drugs to determine which of them can save cells when they are in a problem environment. Such a rapid testing method is called high-performance screening.

Kessler and Bissonnett demonstrated that newly acquired neurons function in the same way as their prototypes. They transplanted them into the hippocampus of mice and showed that the neurons function normally. Cells formed axons, or binding fibers projected into hippocampal structures, and produced acetylcholine, a chemical necessary for the hippocampus to extract memories from other parts of the brain.

In a new, unpublished study, scientists developed another method for obtaining neurons. They transformed human skin cells into embryonic stem cells (the so-called induced pluripotent stem cells, iPS cells), and then reprogrammed them into neurons.

These stem cells and neurons were obtained from the skin cells of three groups of people: patients with Alzheimer's disease, healthy people without a family history of Alzheimer's and healthy people with an increased likelihood of developing this neurodegenerative disease due to a family history of Alzheimer's disease caused by genetic mutations or unknown causes.

"This gives us a new method for studying diseased cells obtained directly from patients with Alzheimer's disease," says Professor Kessler. "That's why it's especially interesting".

Bessonnett's persistence in the face of often disappointing results was fueled by his childhood memories of the dying of Alzheimer's Dede.

"I saw how the disease slowly and mercilessly destroys his memory and personality, and was powerless to help him," recalls Bissonnett. "It made me become a scientist. I wanted to discover new treatments to reverse the damage caused by Alzheimer's disease. My goal was to make human stem cells become new healthy cells, suitable for replacement, so that one day they could be transplanted into the patient's brain and help his memory recover ".

To transform a stem cell into a cholinergic neuron, Bissonnett had to grow and test millions of cells, looking for ways to incorporate a certain sequence of genes.

"A stem cell has the potential to become virtually any cell of the body, from the heart cell to the skin layer," he explains.. "Its development is conditioned by a cascade of events that slowly push it towards the ultimate cellular type".

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