Senior Researcher: 'From these kinds of studies, you can infer what’s going on in a far more detailed way'

Researchers at MIT and Harvard are using new techniques to map changes in brain cells of individuals with Alzheimer’s disease, an MIT press release on a newly-published study said.

Alzheimer's is characterized by deposits of two types of proteins in the brain: tau proteins that form tangles within cells and amyloid-β proteins that create plaques outside cells, the study said. Scientists used a novel technique called STARmap PLUS to investigate how brain cells located near these proteins change as the disease progresses in mice.

The original STARmap was developed by Xiao Wang, a co-senior author of the study. The new version, STARmap PLUS, "is the first to simultaneously map gene expression of individual cells and their location, as well as the spatial distribution of specific proteins in intact tissue samples," the news release said.

Using this technique, researchers were able to study the brain tissue of mice with Alzheimer's at two different stages of the disease in high spatial resolution. "In the earlier stage, they observed a central core of amyloid plaque surrounded by a type of immune cell in the brain called microglia, which are known to play a role in Alzheimer’s," the release said. "The microglia that were closer to the plaques showed genetic signatures that have been linked to neurodegeneration."

They found other brain cells that emerge late in the disease, indicating how brain tissues respond to the presence of the invasive proteins, the release said. 

“This is an exciting improvement on STARmap because we can now co-map the entire transcriptome together with proteins in the same tissue slices, and many diseases involve changes in protein localization and post-transcriptional modifications,” said Wang, according to the press release. 

The scientists also identified outer shells consisting of two other types of brain cells that emerged later in the disease. The discovery will provide valuable insights into how cells respond to these deposits of proteins and could help researchers evaluate current treatments and develop new treatments for Alzheimer's, the release said.

“From these kinds of studies, you can infer what’s going on in a far more detailed way than you could if you just looked at cells from dispersed tissue samples that don’t have their spatial context anymore,” said Morgan Sheng, co-senior author of the study and professor of neuroscience at MIT, according to the press release. “This is a new dimension of transcriptomics, and I think it’s going to be really impactful.” 

Researchers say that the next logical step is to use STARmap PLUS to analyze human brain tissue samples and that the technique could someday be used to study other brain disorders and cancer as well.