Human Hippocampal Neurogenesis Persists in Aged Adults and Alzheimer’s Disease Patients
Open accessAbstract
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.
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The authors' group and others have shown evidence of neurogenesis throughout adulthood using double immunofluorescence, in situ hybridization, and 14C decay-defined neuronal age.
“However, our group and others have shown evidence of neurogenesis throughout adulthood using double immunofluorescence98-101, in situ hybridization102 and 14C decay-defined neuronal age103.”
From Dysregulation of adult hippocampal neuroplasticity in major depression: Pathogenesis and therapeutic implications (2022) · cites this paper as [100]
In a study of 45 Alzheimer's patients aged 52-97, the number of DCX-positive cells declined with neuropathological progression.
“a study including 45 Alzheimer’s patients between 52 and 97 years of age identified that the number of DCX-positive cells declined with the neuropathological progression.431”
From Amyloid β-based therapy for Alzheimer’s disease: Challenges, successes and future (2023) · cites this paper as [431]
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- Authors
- Tobin, M. K., Musaraca, K., Disouky, A., Shetti, A., Bheri, A., Honer, W. G., Kim, N., Dawe, R. J., Bennett, D. A., Arfanakis, K., & Lazarov, O.
- Affiliations
- University of Illinois Chicago (US)
- University of British Columbia (CA)
- Rush University Medical Center (US)
- Corresponding author
- Lazarov, Orly
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 24
- Issue
- 6
- Pages
- 974-982.e3
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC6608595
- OpenAlex
- W2945693197
- Cited by
- 603
- References
- 32
- Citations by year
- 2026: 49 · 2025: 80 · 2024: 84 · 2023: 88 · 2022: 101 · 2021: 89 · 2020: 75 · 2019: 37
- FWCI
- 28.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (CCSG P30 CA060553)
- National Institute on Aging (AG033570-S1, AG062251, AG17917, AG34374, AG060238, AG061628, UH2NS100599)
- National Institutes of Health
- Canadian Institutes of Health Research (MT-14037, MOP-81112)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- hippocampal neurogenesis, adult neurogenesis, aging, Alzheimer's disease, mild cognitive impairment, neural progenitor cells, neuroblasts, immature neurons, nestin, SOX2, doublecortin, PCNA, SNARE proteins, cognitive function, human brain
- MeSH terms
- Doublecortin Domain Proteins, Doublecortin Protein, Aged, 80 and over, Aging, Alzheimer Disease, Cells, Cultured, Cognition, Female, Hippocampus, Humans, Male, Microtubule-Associated Proteins, Neurons, Neuropeptides, Cohort Studies, Proliferating Cell Nuclear Antigen, SNARE Proteins, Neurogenesis, SOXB1 Transcription Factors, Neural Stem Cells, Nestin
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