Dynamic complexity of the microglial activation response in transgenic models of amyloid deposition: Implications for Alzheimer therapeutics

Dave Morgan, Marcia N. Gordon, Jun Tan, Donna Wilcock, Amyn M. Rojiani

Research output: Contribution to journalReview articlepeer-review

156 Scopus citations

Abstract

The presence of activated microglia in postmortem Alzheimer disease specimens is used to support the argument that inflammation contributes to Alzheimer pathogenesis. Transgenic mice overexpressing the amyloid precursor protein (APP) gene form amyloid plaques that are accompanied by local activation of microglia/macrophages in a manner similar to the human disease. Many markers of microglial activation and inflammation increase in an age-dependent manner in these mice. However, manipulation of these inflammatory reactions can lead to unexpected outcomes with several instances of reduced pathology when microglia/macrophages are activated further. In particular, anti-Aβ immunotherapy in amyloid-depositing transgenic mice causes a complex series of changes in microglial markers, negating the implicit belief that such activation is monotonic and represented equally well by any of several "activation" markers. A survey of the peripheral macrophage literature identifies at least 2 distinct activation states of macrophages with different consequences for the surrounding tissue. These different activation states can often be distinguished by the markers that are expressed. Several markers are identified from studies outside the brain that neuroscientists might consider evaluating when attempting to more definitively describe the activation state of the monocyte-derived cells in the brain.

Original languageEnglish (US)
Pages (from-to)743-753
Number of pages11
JournalJournal of Neuropathology and Experimental Neurology
Volume64
Issue number9
DOIs
StatePublished - Sep 2005
Externally publishedYes

Keywords

  • Alzheimer
  • Amyloid
  • Amyloid precursor protein (APP)
  • Apoptosis
  • Inflammation
  • Microglia
  • Necrosis
  • Phagocytosis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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