title: Cortical beta amyloid protein triggers an immune response, but no synaptic changes in the APPswe/PS1dE9 Alzheimer's disease mouse model.
abstract: Using microarray technology we studied the genome-wide gene expression profiles in the frontal cortex of APPswe/PS1dE9 mice and age and sex-matched littermates at the age of 2, 3, 6, 9, 12, and 15-18 months to investigate transcriptional changes that are associated with beta amyloid protein (Aβ) plaque formation and buildup. We observed the occurrence of an immune response with glial activation, but no changes in genes involved in synaptic transmission or plasticity. Comparison of the mouse gene expression data set with a human data set representing the course of Alzheimer's disease revealed a strikingly limited overlap between gene expression in the APPswe/PS1dE9 and human Alzheimer's disease prefrontal cortex. Only plexin domain containing 2, complement component 4b, and solute carrier family 14 (urea transporter) member 1 were significantly upregulated in the mouse and human brain which might suggest a function in Aβ pathology for these 3 genes. In both data sets we detected clusters of upregulated genes involved in immune-related processes. We conclude that the APPswe/PS1dE9 mouse can be a good model to study the immune response associated with cortical Aβ plaques.
authors.affiliation: Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands. k.wirz@nin.knaw.nl
authors.forename: Kerstin T S
authors.initials: KT
authors.lastname: Wirz
authors.forename: Koen
authors.initials: K
authors.lastname: Bossers
authors.forename: Anita
authors.initials: A
authors.lastname: Stargardt
authors.forename: Willem
authors.initials: W
authors.lastname: Kamphuis
authors.forename: Dick F
authors.initials: DF
authors.lastname: Swaab
authors.forename: Elly M
authors.initials: EM
authors.lastname: Hol
authors.forename: Joost
authors.initials: J
authors.lastname: Verhaagen
mesh_terms: D000375:Aging / Q000276:immunology*; D000544:Alzheimer Disease / Q000276:immunology*; D000818:Animals; D004195:Disease Models, Animal; D005625:Frontal Lobe / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000276:immunology*; D009473:Neuronal Plasticity / Q000276:immunology*; D009435:Synaptic Transmission / Q000276:immunology*
chemical_list: D009419:Nerve Tissue Proteins