Mini Brains: Advancing Alzheimer’s Research

In summary, scientists created microscopic “mini-brains” using stem cells to aid in the identification and management of Alzheimer’s disease. Made from human blood, these miniature brains replicate the pathophysiology of Alzheimer’s disease on a smaller scale. With its easier method of diagnosing neurological problems, this cutting-edge technology has the potential to completely transform healthcare, particularly for rural regions.

Important Details:

Novel Approach: “Mini-brains” imitate human brain disease and are produced from stem cells.

Potential for Diagnosis: They might offer a fresh approach to identifying neurological disorders like Alzheimer’s.

Healthcare Impact: By enabling blood sample diagnosis, this device may help isolated communities.

University of Saskatchewan

A researcher at the University of Saskatchewan (USask) is constructing microscopic pseudo-organs from stem cells using a novel approach to aid in the identification and management of Alzheimer’s disease.

Dr. Tyler Wenzel (PhD) could never have imagined how effectively his creations would function when he originally came up with the notion of creating a small brain out of stem cells.

Wenzel’s “mini-brain” has the potential to completely change the way that Alzheimer’s and other brain-related illnesses are identified and managed.

“Never in our wildest dreams did we think that our crazy idea would work,” he said. “These could be used as a diagnostic tool, built from blood.”

Under the guidance of Dr. Darrell Mousseau (PhD), Wenzel, a postdoctoral fellow in the Department of Psychiatry at the College of Medicine, came up with the concept for the “mini-brain,” or more formally, a unique cerebral organoid model.

It is possible to alter human stem cells to create almost any other type of cell in the body. Wenzel was able to develop a tiny artificial organ, about three millimeters square, that looked like someone had tried to smooth out a piece of chewed gum again, thanks to stem cells extracted from human blood.

Making stem cells from a blood sample and turning them into functional brain cells is how these “mini-brains” are constructed. While the idea of using tiny synthetic organoids for research is not new, Wenzel’s lab’s “mini-brains” are special.

The brains from Wenzel’s lab contain four different types of brain cells, whereas the majority of brain organoids only contain neurons, as described in Wenzel’s recent study published in Frontiers of Cellular Neuroscience.

Wenzel’s “mini-brains” have been shown to more closely resemble the functioning adult human brain in tests, making them useful for examining neurological disorders like Alzheimer’s disease in adult patients.

When Wenzel examined those “mini-brains” made from Alzheimer’s patients’ stem cells, he found that the artificial organ had Alzheimer’s disease pathology, albeit on a smaller scale.

“If stem cells can become any cell in the human body, the question then came ‘could we create something that resembles an entire organ?’” Wenzel said.“While we were developing it, I had the crazy idea that if these truly are human brains, if a patient had a disease like Alzheimer’s and we grew their ‘mini-brain,’ in theory that tiny brain would have Alzheimer’s.”

According to Wenzel, this technology can alter how health services are given to Alzheimer’s patients, especially in isolated and rural areas. The Alzheimer Society of Canada has already provided financing for this innovative research.

Instead of requiring patients to travel to hospitals or specialized clinics, Wenzel and his colleagues could develop a consistent method of diagnosing and treating neurological conditions like Alzheimer’s using just a small blood sample, which has a relatively long shelf life and can be couriered. This would relieve patients of a significant burden and save a significant amount of money for the healthcare system.

“In theory, if this tool works the way we think it does, we could just get a blood sample shipped from La Loche or La Ronge to the university and diagnose you like that,” he said.

Wenzel plans to extend the testing to a larger patient pool as a result of the early proof-of-concept work on the “mini-brains” showing great promise.

Additionally, the researchers would like to try to broaden the use of their “mini-brain” research. Wenzel claims that if it can be established that the “mini-brains” accurately represent other neurological disorders or brain diseases, they may be utilized to expedite diagnosis or evaluate the effectiveness of medications on human subjects.

Wenzel cited the lengthy wait periods in Saskatchewan to visit a psychiatrist as an illustration. The time it takes to visit a doctor and get a prescription may be significantly shortened if the “mini-brains” could be utilized to determine which antidepressant works best for a patient with depression.

Wenzel, a former high school science teacher who transitioned into academia, claimed that formulating a hypothesis and hitting the target in an experiment is the “nature of research,” which is what motivates him in his job.

But Wenzel said that he still finds it difficult to comprehend the incredible accomplishment of the first “mini-brains.”

“I’m still in disbelief, but it’s also extremely motivating that something like this happened,” Wenzel said.

“It gives me something that I think will impact society and have actual relevance and create some change … it has a strong potential to shift the landscape of medicine.”

For more information: Brain organoids engineered to give rise to glia and neural networks after 90 days in culture exhibit human-specific proteoforms, Frontiers in Cellular Neuroscience,  https://doi.org/10.3389/fncel.2024.1383688