Aβ increases neural stem cell activity in senescence-accelerated SAMP8 mice

María Díaz-Moreno, Rafael Hortigüela, Ania Gonçalves, Irmina García-Carpio, Gemma Manich, Edurne García-Bermúdez, Mireia Moreno-Estellés, César Eguiluz, Jordi Vilaplana, Carme Pelegrí, Marçal Vilar, Helena Mira*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

28 Citations (Scopus)


Neurogenesis persists in the adult brain as a form of plasticity due to the existence of neural stem cells (NSCs). Alterations in neurogenesis have been found in transgenic Alzheimer's disease (AD) mouse models, but NSC activity and neurogenesis in sporadic AD models remains to be examined. We herein describe a remarkable increase in NSC proliferation in the forebrain of SAMP8, a non-transgenic mouse strain that recapitulates the transition from healthy aging to AD. The increase in proliferation is transient, precedes AD-like symptoms such as amyloid beta 1-42 [Aβ(1-42)] increase or gliosis, and is followed by a steep decline at later stages. Interestingly, invitro studies indicate that secreted Aβ(1-42) and PI3K signaling may account for the early boost in NSC proliferation. Our results highlight the role of soluble Aβ(1-42) peptide and PI3K in the autocrine regulation of NSCs, and further suggest that over-proliferation of NSCs before the appearance of AD pathology may underlie neurogenic failure during the age-related progression of the disease. These findings have implications for therapeutic approaches based on neurogenesis in AD.

Original languageAmerican English
Pages (from-to)2623-2638
Number of pages16
JournalNeurobiology of Aging
Issue number11
Publication statusPublished - Nov 2013


  • Alzheimer's disease
  • Amyloid beta
  • Neural stem cell
  • Neurogenesis
  • Neurosphere
  • Olfactory bulb
  • SAMP8
  • Senescence-accelerated mouse
  • Subventricular zone


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