New brain maps could help the search for Alzheimer's treatments

The search for Alzheimer's treatment could be helped by new brain maps
Click to enlarge the image and toggle caption Allen Institute for Brain Science Allen Institute for Brain Science

A large international group of scientists, including hundreds of others, has created highly detailed maps of brain areas that control movement.

In 17 studies published in Nature, scientists reveal that the maps show the function, appearance, and location of over 100 cell types in the motor cortex of mice, marmoset monkeys and humans.

Researchers expect to use the research to develop improved animal models for human brain diseases such as Alzheimer's or ALS. These scientific findings show that certain cells that are thought to be susceptible to these diseases may not be as vulnerable in humans as they are in animals.

John Ngai, Director of the National Institutes of Health BRAIN initiative which played a key role in funding and organizing the project, said, "To understand how things go wrong we must understand the basic principles."

This huge effort required researchers from many different institutions and labs to collaborate. It was "a new way to do science," said Ed Lein, senior investigator at Seattle's Allen Institute for Brain Science.

A parts list for your brain

This project is part the BRAIN initiative’s Cell Census Network. In 2017, a $250 million effort was launched to create a "parts listing" for human and animal brains. In the end, over 250 scientists from three continents would be involved.

Ngai states that some problems are so complex and large that it requires a city.

Hongkui Zeng (director of the Allen Institute for Brain Science) says that the first step was to take a detailed inventory of all cells found in the human and animal brains.

Zeng says, "To understand the system's workings, you need to first get a parts list for that system, whether it is a car or a computer."

Teams of scientists divided up to classify individual cells by studying their genetics, shapes, and electrical connections. The list included 14 main categories and more than 100 types of cells.

Next, we created a map of each species showing the locations of these parts in the motor cortex. The ultimate goal of the project is to map the entire brain.

Zeng states, "Generating an outline for the motor cortex's function is the first step towards that goal."

Zeng states that a complete map will allow scientists to understand how brain cells "work together to perform a specific function or behavior like moving your arm," Zeng said.

The project already showcases some of the innovative technologies scientists will need in order to achieve that goal. One is to find a way of studying human brain tissue while it is still living.

Transferring brain surgery samples to the laboratory

Many of the labs within the consortium made arrangements with local hospitals to have healthy brain tissue removed by surgeons to treat a tumor or other condition.

Lein states that this tissue is quite healthy and can be used for live experiments to study the properties of cells.

Scientists were able compare brain tissue taken from the operating room to their lab by quickly moving it.

Lein states that cells look remarkably alike overall. However, there are some differences when you look at the finer details.

For instance, mice lack motor cortex brain cells that can make long-distance connections.

Click to enlarge the image and toggle caption Allen Institute for Brain Science Allen Institute for Brain Science

Lein explains that as humans get bigger and more connected to the cortex, the brain becomes larger. "And some of these cells seem to be selectively susceptible in Alzheimer's disease."

Lein believes that this discovery could explain why Alzheimer's drugs that work in mice don't work in humans.

Another discovery was that humans possess a different version if an enormous neuron that is affected by Lou Gehrig's Disease, also known as amytrophic lateral Sclerosis.

These findings are the direct result of scientists working together and sharing what they find," Lein states. Instead of keeping research private until publication, he says.

Lein states, "I hope this is kind of a model to the future because this type work really is more open and accelerates scientific research dramatically."