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Adult Neurogenesis Detected in the Aged and Disease Human Brain

Review ofHuman Hippocampal Neurogenesis Persists in Aged Adults and Alzheimer’s Disease Patientsfrom Cell Stem Cell by Stuart P. Atkinson

Recent research from Sorrells et al. offered evidence of a distinct lack of neurogenesis in the adult human hippocampus beyond adolescence [1], a finding that disagreed with the findings of recent studies in healthy [2-4] and Alzheimer’s disease brains [5]. However, a recent Cell Stem Cell article from the laboratory of Orly Lazarov (University of Illinois at Chicago, USA) now firmly establishes the presence of neurogenesis in the hippocampi of 80- and 90-year old human donor brains and in the brains of patients with mild cognitive impairments and Alzheimer’s disease [6]. Does this new study finally settle the debate?

Tobin at al. examined hippocampal samples isolated from 18 patients between the ages of 79 and 99 to detect the presence of neural progenitor cells (NPCs), neuroblasts, or immature neurons. In contrast to the study of Sorrells et al., the study robustly detected the presence of these cell types in all healthy and diseased hippocampal samples, and identify a possible inverse correlation between cell counts and increased time between patient death and analysis as a possible reason contradictory findings. However, this hypothesis requires further consideration given the relatively small number of samples and the additional analysis of parameters such as fixation time and tissue processing as possible contributing factors to the observed differences.

While these findings confirm ongoing adult neurogenesis, they also revealed varying levels of neurogenesis between different individuals for currently unknown reasons, with elevated levels of neurogenesis associated with better cognitive status and higher levels and functional interactions of critical synaptic proteins previously linked to cognitive decline [7, 8]. Indeed, the authors observed a reduction in neuroblast levels in patients with mild cognitive impairments, thereby establishing a decreasing number of neuroblasts as a potential indicator of early cognitive decline. However, the study failed to report an association between neurogenesis and increased levels of the amyloid deposits or neurofibrillary tangles present in Alzheimer's disease patients.

Overall, this fascinating article highlights the existence of hippocampal neurogenesis in the aged and diseased human brain and a possible association between neurogenesis and cognitive status. The authors now hope to generate a more detailed map of hippocampal cell dynamics throughout the entire human lifespan, discovering the functional significance of neurogenesis in the human brain, and widening the number of samples analyzed to provide a fuller more robust picture of human neurogenesis in the adult, aging, and diseased brain.

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References

  1. Sorrells SF, Paredes MF, Cebrian-Silla A, et al., Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults. Nature 2018;555:377.
  2. Boldrini M, Fulmore CA, Tartt AN, et al., Human Hippocampal Neurogenesis Persists throughout Aging. Cell Stem Cell 2018;22:589-599.e5.
  3. Spalding Kirsty L, Bergmann O, Alkass K, et al., Dynamics of Hippocampal Neurogenesis in Adult Humans. Cell 2013;153:1219-1227.
  4. Tartt AN, Fulmore CA, Liu Y, et al., Considerations for Assessing the Extent of Hippocampal Neurogenesis in the Adult and Aging Human Brain. Cell Stem Cell 2018;23:782-783.
  5. Moreno-Jiménez EP, Flor-García M, Terreros-Roncal J, et al., Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease. Nature Medicine 2019;25:554-560.
  6. Tobin MK, Musaraca K, Disouky A, et al., Human Hippocampal Neurogenesis Persists in Aged Adults and Alzheimer's Disease Patients. Cell Stem Cell 2019;24:974-982.e3.
  7. Ramos-Miguel A, Sawada K, Jones AA, et al., Presynaptic proteins complexin-I and complexin-II differentially influence cognitive function in early and late stages of Alzheimer’s disease. Acta Neuropathologica 2017;133:395-407.
  8. Honer WG, Barr AM, Sawada K, et al., Cognitive reserve, presynaptic proteins and dementia in the elderly. Translational Psychiatry 2012;2:e114.