Human Hippocampal Neurogenesis Persists in Aged Adults and Alzheimer's Disease Patients

Cell Stem Cell. 2019 Jun 6;24(6):974-982.e3. doi: 10.1016/j.stem.2019.05.003. Epub 2019 May 23.


Whether hippocampal neurogenesis persists throughout life in the human brain is not fully resolved. Here, we demonstrate that hippocampal neurogenesis is persistent through the tenth decade of life and is detectable in patients with mild cognitive impairments and Alzheimer's disease. In a cohort of 18 participants with a mean age of 90.6 years, Nestin+Sox2+ neural progenitor cells (NPCs) and DCX+ neuroblasts and immature neurons were detected, but their numbers greatly varied between participants. Nestin+ cells localize in the anterior hippocampus, and NPCs, neuroblasts, and immature neurons are evenly distributed along the anterior to posterior axis. The number of DCX+PCNA+ cells is reduced in mild cognitive impairments, and higher numbers of neuroblasts are associated with better cognitive status. The number of DCX+PCNA+ cells correlates with functional interactions between presynaptic SNARE proteins. Our results suggest that hippocampal neurogenesis persists in the aged and diseased human brain and that it is possibly associated with cognition.

Keywords: Alzheimer’s disease; adult neurogenesis; aging; cognitive dysfunction; human neurogenesis; neural stem cells; neurogenesis in aging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Aging / physiology*
  • Alzheimer Disease / pathology*
  • Cells, Cultured
  • Cognition
  • Cohort Studies
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Female
  • Hippocampus / pathology*
  • Humans
  • Male
  • Microtubule-Associated Proteins / metabolism
  • Nestin / metabolism
  • Neural Stem Cells / physiology*
  • Neurogenesis
  • Neurons / physiology*
  • Neuropeptides / metabolism
  • Proliferating Cell Nuclear Antigen / metabolism
  • SNARE Proteins / metabolism
  • SOXB1 Transcription Factors / metabolism


  • DCX protein, human
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Microtubule-Associated Proteins
  • Nestin
  • Neuropeptides
  • PCNA protein, human
  • Proliferating Cell Nuclear Antigen
  • SNARE Proteins
  • SOX2 protein, human
  • SOXB1 Transcription Factors