Locus ceruleus controls Alzheimer's disease pathology by modulating microglial functions through norepinephrine

Mar 17, 2010Proceedings of the National Academy of Sciences of the United States of America

The brain's norepinephrine system influences Alzheimer's disease by controlling immune cell activity

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Abstract

Norepinephrine deficiency is associated with increased inflammatory responses and reduced microglial functions in Alzheimer's disease models.

  • Norepinephrine stimulation in mouse microglia may suppress the production of inflammatory substances in response to Abeta.
  • Microglial migration and ability to engulf Abeta are increased with norepinephrine stimulation.
  • Degeneration of the locus ceruleus is linked to heightened expression of inflammatory mediators and greater Abeta buildup in APP-transgenic mice.
  • Reduced microglial recruitment to Abeta plaques and diminished phagocytosis are observed in mice lacking norepinephrine.
  • Restoring norepinephrine levels with L-threo-DOPS can reverse impairments in microglial functions caused by norepinephrine depletion.

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