Researchers Create Detailed Gene Activity Map of Brain's Prefrontal Cortex

Key facts

• Scientists mapped gene activity in the prefrontal cortex, the brain region behind the forehead responsible for decision-making, emotional regulation, planning and behaviour adaptation, offering new clarity on Alzheimer's disease, Parkinson's disease and schizophrenia.
• Researchers analysed gene activity in the nuclei of more than 6.3 million brain cells, including neurons, immune cells, blood vessel structures and support cells, using post-mortem samples from 1,494 donors aged from infancy to 108 years.
• The research was led by Dr Panos Roussos, director of the Center for Disease Neurogenomics at the Icahn School of Medicine at Mount Sinai, New York City, and published in Nature and other journals.
• The project was carried out through the PsychAD research consortium and supported by the National Institute on Aging, a branch of the US National Institutes of Health.
• Strong overlaps in gene activity linked to nerve-cell maturation, cellular communication and blood-vessel biology were found across vascular dementia, Lewy body disease, Parkinson's and Alzheimer's, with shared pathways in microglia between Alzheimer's and Parkinson's.
• Molecular shifts were pronounced during early development through adulthood, relatively stable across midlife, and resurged later in life, particularly in support and immune cells.
• Around age 24, a transitional phase occurs after which most cellular populations in the prefrontal cortex stabilise.
• Researchers mapped genetic influences across the activity of over 14,000 genes, linking inherited genetic risks of disorders to specific genes and cell types.
• By examining brain tissue from donors who died at different times of day, the team reconstructed 24-hour cycles of gene activity, finding synchronised clock gene patterns in neurons of younger and middle-aged adults but weaker patterns in older adults.
• Individuals who maintained cognitive health despite substantial Alzheimer's pathology showed differences in energy-related cellular processes, suggesting possible protective mechanisms.