title: Inflammatory changes are tightly associated with neurodegeneration in the brain and spinal cord of the APP/PS1KI mouse model of Alzheimer's disease.
abstract: Inflammatory processes are considered to play an important role in the progression of neurodegenerative changes in Alzheimer's disease (AD). In the present study, we performed a systematic expression analysis of various inflammatory and oxidative stress markers in pre-symptomatic and diseased APP/PS1KI mice. This mouse model has been previously shown to harbor severe pathological alterations, including behavioral deficits, axonal degeneration and hippocampal neuron loss starting at the age of 6 months. While the expression levels of most markers remained unchanged in 2-month-old APP/PS1KI mice, at the age of 6 months different astro- and microglia markers including GFAP, Cathepsin D, members of the Toll-like receptor (Tlr) family, TGFbeta-1 and osteopontin were up-regulated. In addition, oxidative stress markers, including the metallothioneins, were also significantly elevated at that time point. As expected, both brain and spinal cord were affected, the latter showing early activation of GFAP-positive astrocytes and Iba1-positive microglia in white matter fiber tracts, which might contribute to the previously reported axonal defects in this mouse model. These data add further evidence to the assumption that inflammatory processes are tightly associated with axonal degeneration and neuron loss, as is evident in the APP/PS1KI mouse model.
authors.affiliation: Division of Molecular Psychiatry and Alzheimer Ph.D. Graduate School, Department of Psychiatry, University of Goettingen, von-Siebold-Str. 5, 37075 Goettingen, Germany. owirths@uni-goettingen.de
authors.forename: Oliver
authors.initials: O
authors.lastname: Wirths
authors.forename: Henning
authors.initials: H
authors.lastname: Breyhan
authors.forename: Andrea
authors.initials: A
authors.lastname: Marcello
authors.forename: Marie-Caroline
authors.initials: MC
authors.lastname: Cotel
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brück
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Bayer
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D005904:Glial Fibrillary Acidic Protein; D053764:Presenilin-1; D053773:Transforming Growth Factor beta1