Unique transcriptional profiles of adult human immature neurons in healthy aging, Alzheimer’s disease, and cognitive resilience

While rodent studies have highlighted active roles for adult-born immature neurons in the hippocampus under both healthy conditions and in Alzheimer’s disease (AD), evidence from the human brain is limited and lacks detailed molecular characterization.

To address this gap, we performed single-nucleus RNA sequencing in aged healthy, AD and dementia-resilient human hippocampus to probe immature neuronal signatures and gene expression alterations associated with AD pathology and resilience. Employing a novel experimental and computational pipeline, we identified persistent populations of immature neurons across all donor groups, with transcriptional profiles reflecting ‘juvenile’ cellular functions, which are compromised in AD.