The study investigates the relationship between cortical neurons and astrocytes in the human brain, focusing on the prefrontal cortex (dlPFC) of 191 donors aged 22–97 years, including healthy individuals and those with schizophrenia. Using single-nucleus RNA sequencing and latent-factor analysis, the researchers identified a coordinated gene-expression program called the Synaptic Neuron and Astrocyte Program (SNAP). This program involves genes related to synaptic function and cholesterol synthesis in astrocytes, as well as synaptic components in neurons. SNAP expression was reduced in both schizophrenia and aging, suggesting a common mechanism underlying cognitive decline in these conditions. The study also found that SNAP expression was associated with genetic risk factors for schizophrenia, particularly in genes involved in synapse formation and plasticity. The findings highlight the importance of SNAP in understanding normal and pathological brain function and suggest potential therapeutic targets for cognitive deficits in schizophrenia and aging.The study investigates the relationship between cortical neurons and astrocytes in the human brain, focusing on the prefrontal cortex (dlPFC) of 191 donors aged 22–97 years, including healthy individuals and those with schizophrenia. Using single-nucleus RNA sequencing and latent-factor analysis, the researchers identified a coordinated gene-expression program called the Synaptic Neuron and Astrocyte Program (SNAP). This program involves genes related to synaptic function and cholesterol synthesis in astrocytes, as well as synaptic components in neurons. SNAP expression was reduced in both schizophrenia and aging, suggesting a common mechanism underlying cognitive decline in these conditions. The study also found that SNAP expression was associated with genetic risk factors for schizophrenia, particularly in genes involved in synapse formation and plasticity. The findings highlight the importance of SNAP in understanding normal and pathological brain function and suggest potential therapeutic targets for cognitive deficits in schizophrenia and aging.