title: Targeting microglia for the treatment of Alzheimer's disease.
abstract: BACKGROUND
  Activated microglia are associated with the progression of Alzheimer's disease (AD), as well as many other neurodegenerative diseases of aging. Microglia are therefore key targets for therapeutic intervention.
  
  
  METHODS
  β-amyloid (Aβ) deposits activate the complement system, which, in turn, stimulates microglia to release neurotoxic materials. Research has focused primarily on anti-inflammatory agents to temper this toxic effect. More recently there has been a focus on converting microglia from this M1 state to an M2 state in which the toxic effects are reduced and their phagocytic activity toward Aβ enhanced. Studies in transgenic mice have suggested a number of possible anti-inflammatory approaches but they may not always be a good model. An example is vaccination with antibodies to Aβ, which is effective in mouse models, but has repeatedly failed in clinical trials. Biomarker studies indicate that AD commences many years prior to clinical onset.
  
  
  CONCLUSIONS
  A hopeful approach to a disease-modifying treatment of AD is to administer agents that inhibit the inflammatory stimulation of microglia or successfully convert them to an M2 state. However, any such treatment must be started early in the disease.
authors.affiliation: University of British Columbia, Kinsmen Laboratory of Neurological Research , 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3 , Canada mcgeerpl@mail.ubc.ca.
authors.forename: Patrick L
authors.initials: PL
authors.lastname: McGeer
authors.forename: Edith G
authors.initials: EG
authors.lastname: McGeer
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D015415:Biomarkers
keywords: IL-1; IL-6; complement; inflammation; membrane attack complex; phagocytosis; β-amyloid protein