On Sept. 23, 2026, research led by Mount Sinai scientists within the PsychAD Consortium, a large-scale, multidisciplinary initiative launched in 2019 with support from the National Institute on Aging (NIA), is featured in a landmark collection of nine papers published across the Nature family of journals that maps the molecular mechanisms underlying Alzheimer’s disease, Parkinson’s disease, schizophrenia, and other brain disorders.

The coordinated package includes three papers in Nature, three in Nature Communications, and one each in Nature Medicine, Nature Genetics, and Scientific Data. Together, these studies represent one of the largest and most comprehensive applications of single-cell genomics to human brain disease research and establish foundational resources expected to accelerate discovery across neuroscience.

The PsychAD Consortium brings together investigators from across the United States and around the world to better understand the biological mechanisms underlying Alzheimer’s disease and related neuropsychiatric disorders. By studying human brain tissue at unprecedented scale and single-cell resolution, researchers have identified both shared and disease-specific molecular changes that contribute to neurodegeneration, psychiatric illness, and cognitive decline.

“Until now, efforts to apply single-cell technology in psychiatry have been relatively small-scale or just focused on individual diseases,” said Panos Roussos, MD, PhD, Mount Sinai Professor of Translational Psychiatry at the Icahn School of Medicine at Mount Sinai, Director of the Center for Disease Neurogenomics, and Contact Principal Investigator of the PsychAD Consortium. “No one has systematically examined how molecular mechanisms overlap across different brain disorders at this scale.”

“By describing the genetic and cellular architecture across many brain disorders, we have started building a pathway toward new treatment targets and the next generation of therapies for these diseases,” added Dr. Roussos, who also serves as Director of the Center for Precision Medicine and Translational Therapeutics at the James J. Peters VA Medical Center in the Bronx.

“This extraordinary collection of studies reflects the scale of the scientific collaboration and discovery that the PsychAD Consortium has made possible,” said Eric J. Nestler, MD, PhD, Anne and Joel Ehrenkranz Dean, Icahn School of Medicine at Mount Sinai. “We are particularly proud to see so many Mount Sinai investigators playing leading roles across this coordinated body of work, which brings together data from thousands of human brains and millions of individual cells. Truly a tour de force of modern neuroscience, these studies demonstrate how large-scale, collaborative approaches can deepen our understanding of the biological mechanisms underlying brain disorders and create valuable resources for the broader scientific community.”

At the center of the collection is a landmark Nature study that generated a population-scale single-cell atlas of the human dorsolateral prefrontal cortex using more than 6.3 million cell nuclei from 1,494 human donors spanning Alzheimer’s disease, Parkinson’s disease, Lewy body disease, vascular dementia, schizophrenia, bipolar disorder, and neurotypical controls. The study identified both shared and disease-specific molecular programs across neuronal, glial, immune, and vascular cell types and defined cellular trajectories associated with disease progression and neuropsychiatric symptoms.

“By analyzing millions of cells across multiple brain disorders, we found that many diseases share common molecular pathways while also exhibiting distinct cellular signatures,” said Donghoon Lee, PhD, Assistant Professor of Psychiatry, and Genetics and Genomic Sciences, at the Icahn School of Medicine at Mount Sinai, and first and co-corresponding author of the Nature study. “These findings provide a framework for understanding why different neurological and psychiatric disorders converge on similar biological processes while maintaining distinct disease-specific features.”

The atlas establishes one of the largest single-cell datasets ever assembled for human brain disease research, providing investigators worldwide with a foundational resource for understanding how cellular and molecular mechanisms contribute to neurological and psychiatric disease. “Our goal is for this resource to accelerate the development of targeted therapies by helping researchers better understand the molecular complexity underlying brain disorders,” added Dr. Lee.