title: An integrated proteomics approach shows synaptic plasticity changes in an APP/PS1 Alzheimer's mouse model.
abstract: The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. We report that signalling pathways related to synaptic functions associated with dendritic spine morphology, neurite outgrowth, long-term potentiation, CREB signalling and cytoskeletal dynamics were altered in 12 month old APPswe/PS1ΔE9 mice, particularly in the neocortex and olfactory bulb. This was associated with cerebral amyloidosis as well as formation of argyrophilic tangle-like structures and microglial clustering in all brain regions, except for brainstem. These responses may be epigenetically modulated by the interaction with a number of miRNAs regulating spine restructuring, Aβ expression and neuroinflammation.We suggest that these changes could be associated with development of cognitive dysfunction in early disease states in patients with Alzheimer's disease.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Kempf
authors.affiliation: Institute of Molecular Medicine, University of Southern Denmark, Odense C, Denmark.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Metaxas
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark.
authors.forename: María
authors.initials: M
authors.lastname: Ibáñez-Vea
authors.affiliation: Department of Medical Neuroscience, Dalhousie University, Halifax, NS, Canada.|Department of Medicine (Neurology and Geriatric Medicine), Dalhousie University, Halifax, NS, Canada.
authors.forename: Sultan
authors.initials: S
authors.lastname: Darvesh
authors.affiliation: Institute of Molecular Medicine, University of Southern Denmark, Odense C, Denmark.
authors.forename: Bente
authors.initials: B
authors.lastname: Finsen
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Larsen
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity; D040901:Proteomics / Q000379:methods
keywords: Pathology Section; miRNA; neuroinflammation; proteomics; synapse; tau protein