Less than ten years ago, Dr. Hansruedi Mathys undertook a challenging project to catalog all the gene readouts from 100 brain cells, a task that seemed overwhelming at the time.
With recent technological progress, Dr. Mathys has successfully mapped out these ‘transcriptomes’ not just from 100, but from 1.3 million brain cortex cells of 48 individuals, both with and without Alzheimer’s disease.
Dr. Mathys, a pioneer in single-cell transcriptomic analysis on post-mortem human brain tissue and an assistant professor of neurobiology at the University of Pittsburgh School of Medicine, believes that this atlas of the aging human brain provides valuable molecular insights into the brain’s vulnerability and resilience.
He expresses his interest in understanding cognitive resilience, a state where individuals exhibit no cognitive impairments despite typical Alzheimer’s tissue pathology. Recent discoveries from the study have raised hopes of potentially inducing such resilience artificially in individuals predisposed to memory loss.
In their recently published study in Nature, Dr. Mathys and his colleagues at the Massachusetts Institute of Technology examined transcriptomes of cells from six brain regions commonly impacted by Alzheimer’s. The resulting atlas, now accessible online to researchers worldwide, can aid in gene and molecular research related to brain health.
Through tracking how transcriptomic changes relate to cognitive decline and Alzheimer’s pathology, Dr. Mathys and his team found that astrocytes, essential brain tissue cells with various critical functions, may play a crucial role in cognitive resilience. Dr. Mathys plans to further investigate altering astrocyte metabolic pathways to impact cognitive function based on the findings from the transcriptome mapping.
Dr. Mathys emphasizes that while this project provides valuable insights, there is still a wealth of knowledge to gain about Alzheimer’s disease and the human brain, asserting that this study is just the initial step in a broader research journey.
