Activation of innate immune cGAS-STING pathway contributes to Alzheimer’s pathogenesis in 5×FAD mice

Apr 28, 2023Nature aging

Activation of the innate immune cGAS-STING pathway linked to Alzheimer's development in 5×FAD mice

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Abstract

The cGAS-STING pathway is activated in the brains of human Alzheimer's disease patients and aged mice.

  • The binding of double-stranded DNA by cGAS was detected in the cytoplasm of affected brain cells.
  • Activation of the cGAS-STING pathway in microglia was observed in Alzheimer's disease models.
  • Cgas;5×FAD mice showed significant protection against cognitive decline and associated Alzheimer's pathology.
  • Deficiency of Cgas in microglia reduced neurotoxic effects related to amyloid-β peptides.
  • Inhibition of STING using H-151 effectively reduced the activation of the cGAS-STING pathway and improved Alzheimer's disease symptoms in mice.

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