Failure of Alzheimer’s Mice Brain Resident Neural Precursor Cells in Supporting Microglia-Mediated Amyloid β Clearance

Marva Lachish, Nina Fainstein, Tal Ganz, Lihi Sofer, Tamir Ben-Hur*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The failure of brain microglia to clear excess amyloid β (Aβ) is considered a leading cause of the progression of Alzheimer’s disease pathology. Resident brain neural precursor cells (NPCs) possess immune-modulatory and neuro-protective properties, which are thought to maintain brain homeostasis. We have recently showed that resident mouse brain NPCs exhibit an acquired decline in their trophic properties in the Alzheimer’s disease brain environment. Therefore, we hypothesized that functional NPCs may support microglial phagocytic activity, and that NPCs derived from the adult AD mouse brain may fail to support the clearance of Aβ by microglia. We first identified in the AD brain, in vivo and ex vivo, a subpopulation of microglia that express high Aβ phagocytic activity. Time-lapse microscopy showed that co-culturing newborn NPCs with microglia induced a significant increase in the fraction of microglia with high Aβ phagocytic activity. Freshly isolated NPCs from adult wild type, but not AD, mouse brain, induced an increase in the fraction of microglia with high Aβ phagocytic activity. Finally, we showed that NPCs also possess the ability to promote Aβ degradation within the microglia with high Aβ phagocytic activity. Thus, resident brain NPCs support microglial function to clear Aβ, but NPCs derived from the AD environment fail to do so. We suggest that the failure of AD brain NPCs to support Aβ clearance from the brain by microglia may accelerate disease pathology.

Original languageAmerican English
Article number876
JournalCells
Volume11
Issue number5
DOIs
StatePublished - 1 Mar 2022

Bibliographical note

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Alzheimer’s disease
  • Amyloid β
  • Degradation
  • Microglia
  • Neural precursor cells
  • Phagocytosis

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