Human amyloid β-induced neuroinflammation is an early event in neurodegeneration

Jeffrey M. Craft, D. Martin Watterson, Linda J. Van Eldik

Research output: Contribution to journalArticlepeer-review

98 Scopus citations


Using a human amyloid β (Aβ) intracerebroventricular infusion mouse model of Alzheimer's disease-related injury, we previously demonstrated that systemic administration of a glial activation inhibitor could suppress neuroinflammation, prevent synaptic damage, and attenuate hippocampal-dependent behavioral deficits. We report that Aβ-induced neuroinflammation is an early event associated with onset and progression of pathophysiology, can be suppressed by the glial inhibitor over a range of intervention start times, and is amenable to suppression without inhibiting peripheral tissue inflammatory responses. Specifically, hippocampal neuroinflammation and neurodegeneration occur in close time proximity at 4-6 weeks after the start of infusion. Intraperitoneal administration of inhibitor for 2-week intervals starting at various times after initiation of Aβ infusion suppresses progression of pathophysiology. The glial inhibitor is a selective suppressor of neuroinflammation, in that it does not block peripheral tissue production of proinflammatory cytokines or markers of B- and T-cell activation after a systemic lipopolysaccharide challenge. These results support a causal link between neuroinflammation and neurodegeneration, have important implications for future therapeutic development, and provide insight into the relative time window for targeting neuroinflammation with positive neurological outcomes.

Original languageEnglish
Pages (from-to)484-490
Number of pages7
Issue number5
StatePublished - Apr 1 2006


  • Alzheimer's disease
  • Animal model
  • Cytokine
  • Drug discovery
  • Glia activation
  • Immunosuppression

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience


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