Normally, if a person has Alzheimer’s disease pathology in their brain, it would be reflected in impaired cognition. But there is a small subset of “resilient” individuals with Alzheimer’s pathology who never showed any symptoms of the disease while they were alive. Hansruedi Mathys, assistant professor of neurobiology in the School of Medicine, is mapping the brain to determine what distinguishes these resilient individuals from those who are not resilient.
To accomplish this goal, Mathys used a method known as single-cell transcriptomic analysis, examining RNA in individual cell nuclei. Previously, the standard method took an average of all cells in a frozen brain tissue sample, which did not allow researchers to differentiate between cell types.
“If we combine all cell types and look at the average, we have to infer what genes are expressed. The average may not reflect the reality of what happens in any one cell,” Mathys says. “But if you can measure the gene expression in individual cells, you get much more powerful, granular information.”
“Our recent findings have made me more hopeful than ever that it might be possible to therapeutically induce such resilience in people who would otherwise be susceptible to memory loss.”
Mathys and a team from the Massachusetts Institute of Technology used this single-cell analysis to create an atlas as a tool for gene and molecular discovery. They analyzed the transcriptomes of individual cells across six different brain regions, focusing on pathways affecting brain health.
“I am extremely interested in understanding the phenomenon of cognitive resilience, where, despite the characteristic signs of Alzheimer’s tissue pathology, individuals display no cognitive impairment,” Mathys says. “Our recent findings have made me more hopeful than ever that it might be possible to therapeutically induce such resilience in people who would otherwise be susceptible to memory loss.”