title: Aging, microglia and cytoskeletal regulation are key factors in the pathological evolution of the APP23 mouse model for Alzheimer's disease.
abstract: Aging is the key risk factor for Alzheimer's disease (AD). In addition, the amyloid-beta (Aβ) peptide is considered a critical neurotoxic agent in AD pathology. However, the connection between these factors is unclear. We aimed to provide an extensive characterization of the gene expression profiles of the amyloidosis APP23 model for AD and control mice and to evaluate the effect of aging on these profiles. We also correlated our findings to changes in soluble Aβ-levels and other pathological and symptomatic features of the model. We observed a clear biphasic expression profile. The first phase displayed a maturation profile, which resembled features found in young carriers of familial AD mutations. The second phase reflected aging processes and showed similarities to the progression of human AD pathology. During this phase, the model displayed a clear upregulation of microglial activation and lysosomal pathways and downregulation of neuron differentiation and axon guidance pathways. Interestingly, the changes in expression were all correlated to aging in general, but appeared more extensive/accelerated in APP23 mice.
authors.affiliation: Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Leen
authors.initials: L
authors.lastname: Janssen
authors.affiliation: Department of Neuroscience, Medical Physiology Section, University of Groningen, University Medical Center Groningen (UMCG), Groningen, The Netherlands.
authors.forename: Marissa L
authors.initials: ML
authors.lastname: Dubbelaar
authors.affiliation: Department of Neuroscience, Medical Physiology Section, University of Groningen, University Medical Center Groningen (UMCG), Groningen, The Netherlands.
authors.forename: Inge R
authors.initials: IR
authors.lastname: Holtman
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands.
authors.forename: Jelkje
authors.initials: J
authors.lastname: de Boer-Bergsma
authors.affiliation: Department of Neuroscience, Medical Physiology Section, University of Groningen, University Medical Center Groningen (UMCG), Groningen, The Netherlands.
authors.forename: Bart J L
authors.initials: BJ
authors.lastname: Eggen
authors.affiliation: Department of Neuroscience, Medical Physiology Section, University of Groningen, University Medical Center Groningen (UMCG), Groningen, The Netherlands.
authors.forename: Hendrikus W G M
authors.initials: HW
authors.lastname: Boddeke
authors.affiliation: Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium; University of Groningen, University Medical Center Groningen (UMCG), Department of Neurology and Alzheimer Research Center, Groningen, The Netherlands; Biobank, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Peter P
authors.initials: PP
authors.lastname: De Deyn
authors.affiliation: Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium. Electronic address: debby.vandam@uantwerpen.be.
authors.forename: Debby
authors.initials: D
authors.lastname: Van Dam
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003599:Cytoskeleton / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D053263:Gene Regulatory Networks; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism / Q000473:pathology*; D009154:Mutation; D059467:Transcriptome
chemical_list: D016564:Amyloid beta-Protein Precursor
keywords: APP23 mouse model; Alzheimer's disease; Amyloid; Gene expression; Inflammation; RNA sequencing