What it is
Researchers profiled 355,997 cell nuclei from post-mortem human hippocampi spanning five cohorts: young adults with intact memory, aged adults without cognitive impairment, aged adults with exceptional memory (SuperAgers), adults with preclinical intermediate pathology, and adults with Alzheimer's disease. Using paired single-nucleus RNA sequencing and chromatin accessibility profiling, they identify neural stem cells, neuroblasts and immature granule neurons, showing that neurogenesis persists in the adult human hippocampus. Dysregulated neurogenesis tracks largely with changes in chromatin accessibility, and neurogenic cells from people with preclinical Alzheimer's already show altered accessibility that becomes more pronounced in established disease. SuperAgers carry a distinct neurogenic profile the authors describe as a resilience signature.
Why it matters
Whether the adult human hippocampus generates new neurons has been disputed for decades, and the molecular networks that regulate the process were poorly understood. Resolving neurogenic cell states directly in human tissue across five cohorts shows where the process is altered before cognitive symptoms appear.
How to read this
Chromatin-level changes in neurogenic cells that precede clinical Alzheimer's point to an early window and a molecular axis distinguishing cognitive resilience from decline.
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