Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease View Full Text


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Article Info

DATE

2019-04

AUTHORS

Elena P. Moreno-Jiménez, Miguel Flor-García, Julia Terreros-Roncal, Alberto Rábano, Fabio Cafini, Noemí Pallas-Bazarra, Jesús Ávila, María Llorens-Martín

ABSTRACT

The hippocampus is one of the most affected areas in Alzheimer's disease (AD)1. Moreover, this structure hosts one of the most unique phenomena of the adult mammalian brain, namely, the addition of new neurons throughout life2. This process, called adult hippocampal neurogenesis (AHN), confers an unparalleled degree of plasticity to the entire hippocampal circuitry3,4. Nonetheless, direct evidence of AHN in humans has remained elusive. Thus, determining whether new neurons are continuously incorporated into the human dentate gyrus (DG) during physiological and pathological aging is a crucial question with outstanding therapeutic potential. By combining human brain samples obtained under tightly controlled conditions and state-of-the-art tissue processing methods, we identified thousands of immature neurons in the DG of neurologically healthy human subjects up to the ninth decade of life. These neurons exhibited variable degrees of maturation along differentiation stages of AHN. In sharp contrast, the number and maturation of these neurons progressively declined as AD advanced. These results demonstrate the persistence of AHN during both physiological and pathological aging in humans and provide evidence for impaired neurogenesis as a potentially relevant mechanism underlying memory deficits in AD that might be amenable to novel therapeutic strategies. More... »

PAGES

1-7

References to SciGraph publications

  • 2006-10. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry in ACTA NEUROPATHOLOGICA
  • 2014-04. Performance on a pattern separation task by Alzheimer’s patients shows possible links between disrupted dentate gyrus activity and apolipoprotein E ∈4 status and cerebrospinal fluid amyloid-β42 levels in ALZHEIMER'S RESEARCH & THERAPY
  • 2013-04. GSK-3β overexpression causes reversible alterations on postsynaptic densities and dendritic morphology of hippocampal granule neurons in vivo in MOLECULAR PSYCHIATRY
  • 2018-03. Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults in NATURE
  • 2006-12. Variability of doublecortin-associated dendrite maturation in adult hippocampal neurogenesis is independent of the regulation of precursor cell proliferation in BMC NEUROSCIENCE
  • 2017-12. Absence of CX3CR1 impairs the internalization of Tau by microglia in MOLECULAR NEURODEGENERATION
  • 2011-04. Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation in NATURE
  • 2007-03. Young and excitable: new neurons in memory networks in NATURE NEUROSCIENCE
  • 2014-10. Peripherally triggered and GSK-3β-driven brain inflammation differentially skew adult hippocampal neurogenesis, behavioral pattern separation and microglial activation in response to ibuprofen in TRANSLATIONAL PSYCHIATRY
  • 1998-11. Neurogenesis in the adult human hippocampus in NATURE MEDICINE
  • 2018-07. Hippocampal neurogenesis confers stress resilience by inhibiting the ventral dentate gyrus in NATURE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41591-019-0375-9

    DOI

    http://dx.doi.org/10.1038/s41591-019-0375-9

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1112969620

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30911133


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