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S4‐02‐03: COMPLEMENT IN ALZHEIMER'S DISEASE: LESSONS FROM C3‐DEFICIENT MICE
Author(s) -
Lemere Cynthia A.,
Shi Qiaoqiao,
Caldarone Barbara,
Chowdhury Saba,
Ma Rong,
Hong Soyon,
Stevens Beth
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.04.360
Subject(s) - microglia , neurogenesis , hippocampus , barnes maze , open field , elevated plus maze , morris water navigation task , complement system , neuroscience , immune system , medicine , endocrinology , psychology , immunology , inflammation , spatial learning , anxiety , psychiatry
Background: Generation of neurotoxic amyloid-ß peptides and their deposition along with neurofibrillary tangle formation represent key pathological hallmarks in Alzheimer’s disease (AD). Recent evidence suggests that inflammation may be a third important component which, once initiated in response to neurodegeneration or dysfunction actively contributes to disease progression and chronicity. Microglia is being activated by binding of aggregated proteins or aberrant nucleic acids to pattern recognition receptors which elicit an innate immune response. The latter is characterized by the release of in€ıflammatory mediators including complement activators and inhibitors, chemokines, cytokines, radical oxygen species and enzyme systems. Exogenous as well as endogenous factors may promote and facilitate neuroinflammation in the AD brain. Thus, degeneration of aminergic brain stem nuclei including the locus ceruleus and the nucleus basalis of Meynert may drive inflammation in their projection areas given the antiinflammatory and neuroprotective action of their key transmitters norepinephrine and acetylcholine. Methods: Analysis of neuroinflammatio and in particular of micro and astroglial cell function in vitro and in vivo. Determination of inflammatory markes from cell culture, murine mouse brain and brain tissue or cerebrospinal fluid of MCI and AD patients. Results: In inflammation may not just occur secondary to degeneration, but actively drive amyloid beta aggregation and APP processing. Inhibition of themicroglia driven innate immune response at key signalling steps may provide protection. Conclusions: Therefore, antiinflammatory treatment strategies should be considered. Data on microglial activation in AD along with suggestions to modify and alter the prointo an antiinflammatory phenotype will be reviewed and discussed.