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Augmenting neurogenesis rescues memory impairments in Alzheimer's disease by restoring the memory-storing neurons.

The Journal of experimental medicine | 2022

Hippocampal neurogenesis is impaired in Alzheimer's disease (AD) patients and familial Alzheimer's disease (FAD) mouse models. However, it is unknown whether new neurons play a causative role in memory deficits. Here, we show that immature neurons were actively recruited into the engram following a hippocampus-dependent task. However, their recruitment is severely deficient in FAD. Recruited immature neurons exhibited compromised spine density and altered transcript profile. Targeted augmentation of neurogenesis in FAD mice restored the number of new neurons in the engram, the dendritic spine density, and the transcription signature of both immature and mature neurons, ultimately leading to the rescue of memory. Chemogenetic inactivation of immature neurons following enhanced neurogenesis in AD, reversed mouse performance, and diminished memory. Notably, AD-linked App, ApoE, and Adam10 were of the top differentially expressed genes in the engram. Collectively, these observations suggest that defective neurogenesis contributes to memory failure in AD.

Pubmed ID: 35984475 RIS Download

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: NIA NIH HHS, United States
    Id: R01 AG076940
  • Agency: NIA NIH HHS, United States
    Id: R01 AG062251
  • Agency: NCATS NIH HHS, United States
    Id: UL1 TR002003
  • Agency: NIA NIH HHS, United States
    Id: R01 AG033570
  • Agency: NIAAA NIH HHS, United States
    Id: R01 AA027766
  • Agency: NIA NIH HHS, United States
    Id: R01 AG060238
  • Agency: NIA NIH HHS, United States
    Id: RF1 AG033570
  • Agency: NIA NIH HHS, United States
    Id: R21 AG061628

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