title: Neuroinflammation and related neuropathologies in APPSL mice: further value of this in vivo model of Alzheimer's disease.
abstract: BACKGROUND
  Beyond cognitive decline, Alzheimer's disease (AD) is characterized by numerous neuropathological changes in the brain. Although animal models generally do not fully reflect the broad spectrum of disease-specific alterations, the APPSL mouse model is well known to display early plaque formation and to exhibit spatial learning and memory deficits. However, important neuropathological features, such as neuroinflammation and lipid peroxidation, and their progression over age, have not yet been described in this AD mouse model.
  
  
  METHODS
  Hippocampal and neocortical tissues of APPSL mice at different ages were evaluated. One hemisphere from each mouse was examined for micro- and astrogliosis as well as concomitant plaque load. The other hemisphere was evaluated for lipid peroxidation (quantified by a thiobarbituric acid reactive substances (TBARS) assay), changes in Aβ abundance (Aβ38, Aβ40 and Aβ42 analyses), as well as determination of aggregated Aβ content (Amorfix A4 assay). Finally, correlation analyses were performed to illustrate the time-dependent correlation between neuroinflammation and Aβ load (soluble, insoluble, fibrils), or lipid peroxidation, respectively.
  
  
  RESULTS
  As is consistent with previous findings, neuroinflammation starts early and shows strong progression over age in the APPSL mouse model. An analyses of concomitant Aβ load and plaque deposition revealed a similar progression, and high correlations between neuroinflammation markers and soluble or insoluble Aβ or fibrillar amyloid plaque loads were observed. Lipid peroxidation, as measured by TBARS levels, correlates well with neuroinflammation in the neocortex but not the hippocampus. The hippocampal lipid peroxidation correlated strongly with the increase of LOC positive fiber load, whereas neocortical TBARS levels were unrelated to amyloidosis.
  
  
  CONCLUSIONS
  These data illustrate for the first time the progression of major AD related neuropathological features other than plaque load in the APPSL mouse model. Specifically, we demonstrate that microgliosis and astrocytosis are prominent aspects of this AD mouse model. The strong correlation of neuroinflammation with amyloid burden and lipid peroxidation underlines the importance of these pathological factors for the development of AD. The new finding of a different relation of lipid peroxidation in the hippocampus and neocortical regions show that the model might contribute to the understanding of complex pathological mechanisms and their interplay in AD.
authors.forename: Tina
authors.initials: T
authors.lastname: Löffler
authors.forename: Stefanie
authors.initials: S
authors.lastname: Flunkert
authors.forename: Daniel
authors.initials: D
authors.lastname: Havas
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schweinzer
authors.forename: Marni
authors.initials: M
authors.lastname: Uger
authors.forename: Manfred
authors.initials: M
authors.lastname: Windisch
authors.forename: Ernst
authors.initials: E
authors.lastname: Steyrer
authors.affiliation: QPS-Austria GmbH, Parkring 12, 8074 Grambach, Austria. Birgit.hutter-paier@qps.com.
authors.forename: Birgit
authors.initials: B
authors.lastname: Hutter-Paier
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004660:Encephalitis / Q000209:etiology* / Q000473:pathology; D005786:Gene Expression Regulation / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D019579:Neocortex / Q000473:pathology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D017392:Thiobarbituric Acid Reactive Substances