Caudate nucleus aging and its association with brain disorders

Single-nucleus caudate atlases from 178 human donors and six rhesus macaques show that neuron-to-neuron communication declines with age, with larger declines in alcohol use disorder (AUD).

• Why it matters: Aging reshapes caudate cell types, but how these changes map onto substance use and psychiatric or neurodegenerative disorders is unclear.
• What they did: The study built single-nucleus transcriptomic atlases (963,842 human nuclei; 83,699 macaque nuclei) and integrated bulk RNA-seq (3,139 profiles) plus paired RNA and chromatin accessibility from 257,524 caudate nuclei across 161 control and AUD donors.
• The result: Glial aging features were shared across species, while neuronal changes diverged; nonlinear late-adulthood shifts and earlier AUD trajectories implicated mitochondrial function and fatty acid metabolism across AUD, OUD, bipolar disorder, schizophrenia, and Alzheimer disease.

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