The Complexity of the Human Brain, as Revealed by its Microglia Cells and Analogs to Alzheimer’s Disease

“Prior to this data set, it was just a hypothesis that the brain was really complicated,” adds Amy Bernard, the director of life sciences at the Kavli Foundation, who was not involved in this project. It’s now possible to see the diversity of cells, which will help us figure out how to solve the problem. But the brain’s wiring doesn’t say anything about what its individual units are made of. To understand what makes brain cells diverse, Lein says that neuroscientists are borrowing tricks from the genomics world.

Historically, it’s been nearly impossible to get a handle on the complexity of the human brain. With so many interconnected pieces, “it’s not really a single organ—it’s like a thousand organs,” says Ed Lein, a senior investigator at the Allen Institute for Brain Science who helped lead the atlas project.

Ren and his colleagues have used cell type to predict how the genetic switches may affect gene regulation and the risk of neurological diseases. For instance, in cells called microglia , which clear away dead or damaged cells, the presence of some genetic switches was strongly linked to risks of Alzheimer’s disease. It is possible to test for genes that contribute to the start of a disease. “This is made possible because we have — for the first time — delineated the genetic switches for hundreds of different cell types,” says Ren.

Ren says that the next step is for the BICCN team to sequence even more brain cells. Researchers will work with more tissue samples to get a sense of how the human brain varies depending on age and population. “This is only the beginning,” says Ren.