Integrating over 1 million single-cell sequencing datasets from the prefrontal cortex reveals cell-type-specific alterations in neurotransmitter systems across aging and eight neuropsychiatric disorders. These dysregulated patterns differ by disease and sex, identifying mechanisms that could guide therapeutic targeting and establish a foundation for precision medicine approaches in CNS disease.
Key Points
- Neurotransmitter system remodeling is disease-specific and age-dependent across cell types
- Sex differences in neurotransmitter dysregulation emerge as distinct disease biomarkers
- Multi-omics integration identifies targetable NTS networks for precision CNS therapeutics
Longevity Analysis
Neurotransmitter dysregulation is a central driver of cognitive decline and neuropsychiatric disease in aging. This work demonstrates that the prefrontal cortex undergoes systematic remodeling of neurotransmitter receptors and transporters—molecular infrastructure that governs mental clarity, emotional regulation, and stress tolerance. By mapping these changes across the lifespan and across disease states, the research reveals that interventions targeting neurotransmitter systems must account for both age and individual disease context. This moves beyond generic dopamine or serotonin-focused approaches toward cell-type-specific and disease-calibrated strategies. The inclusion of sex differences further clarifies why symptom trajectories and treatment responses diverge between men and women, enabling more granular selection of therapeutic candidates early in the disease process—critical for preserving cognitive and emotional function across the decades.
Original published by Wiley Aging Cell, by Rui‐Ze Niu, Meng‐Yuan Zhang, Yan‐Ping Li, Xiao‐Qian Zhou, Xiao‐Lei Liu, Jie Wu, Wei‐Wei Wang, Yan‐Jun Wang, Yi Ruan, Yu Ding, Xiao‐Feng Zeng, Tian‐Hao Bao .