Landmark map of human brain’s gene activity holds clues to Alzheimer’s disease and more

Key Points:

• Researchers have created the largest map to date of gene activity in the human prefrontal cortex, analyzing over six million individual cells from nearly 1,500 people to advance the study of neurodegenerative and psychiatric diseases.
• The study, published across eight papers including three in Nature, was led by the PsychAD Consortium, which began in 2019 to link genetic variation, aging, and disease to specific brain cell changes.
• The focus on the dorsolateral prefrontal cortex is due to its key role in executive functions like planning and multitasking, with disruptions in this area linked to psychiatric disorders and dementia.
• The research included brain tissue from donors of diverse ages and ancestries, covering neurotypical individuals and those diagnosed with eight brain disorders such as Alzheimer’s, Parkinson’s, schizophrenia, and bipolar disorder.
• Using single-cell RNA sequencing, the team detailed gene activity in neurons, immune cells, and vascular cells, providing unprecedented insight into brain cell function and disease mechanisms, though further studies on other brain regions are needed for a complete understanding.