Human hippocampal neurogenesis in adulthood, ageing and Alzheimer's disease.
Level 4 - case-series / case-control
Cross-sectional post-mortem human tissue comparison across defined cognitive and clinical cohorts.
PubMed 41741649 · doi:10.1038/s41586-026-10169-4
What was done
Authors performed multiomic single-cell analysis combining single-nucleus RNA sequencing (snRNA-seq) and single-nucleus ATAC-seq on 355,997 nuclei isolated from post-mortem human hippocampi. The samples spanned five distinct groups: young adults with intact memory, cognitively unimpaired older adults, older adults with extraordinary memory capacity (SuperAgers), adults with preclinical intermediate Alzheimer's pathology, and adults with diagnosed Alzheimer's disease. Profiles were evaluated to identify cell types—including neural stem cells, neuroblasts, and immature granule neurons—and analyze group-specific transcription factor signatures and chromatin accessibility.
What was found
The study profiled 355,997 nuclei and confirmed the presence of neural stem cells, neuroblasts, and immature granule neurons in adult human hippocampi. Dysregulated neurogenesis correlated with alterations in chromatin accessibility, which were detectable early in individuals with preclinical Alzheimer's disease and became more prominent in established Alzheimer's disease. SuperAgers exhibited a distinct neurogenesis profile indicative of cognitive resilience, while shifts in astrocyte and CA1 neuronal profiles were linked to hippocampal cognitive function. The abstract reports no numerical effect sizes, variance estimates, or p-values.
Why it matters
This study provides molecular evidence that adult human hippocampal neurogenesis persists across the lifespan and defines epigenetic and transcriptional signatures linked to cognitive resilience in SuperAgers and early vulnerability in preclinical Alzheimer's disease.
Limits
The total number of human donors is not specified in the abstract. The post-mortem, cross-sectional design captures only single time-point snapshots, precluding direct tracking of dynamic neurogenic flux or causal verification in living humans. No quantitative effect sizes, fold changes, or statistical confidence intervals are provided in the abstract.
Cited by
- supports Neurogenesis, the development of new brain cells, continues into older adulthood and does not completely stop at a certain age.