title: Early alterations in functional connectivity and white matter structure in a transgenic mouse model of cerebral amyloidosis.
abstract: Impairment of brain functional connectivity (FC) is thought to be an early event occurring in diseases with cerebral amyloidosis, such as Alzheimer's disease. Regions sustaining altered functional networks have been shown to colocalize with regions marked with amyloid plaques burden suggesting a strong link between FC and amyloidosis. Whether the decline in FC precedes amyloid plaque deposition or is a consequence thereof is currently unknown. The sequence of events during early stages of the disease is difficult to capture in humans due to the difficulties in providing an early diagnosis and also in view of the heterogeneity among patients. Transgenic mouse lines overexpressing amyloid precursor proteins develop cerebral amyloidosis and constitute an attractive model system for studying the relationship between plaque and functional changes. In this study, ArcAβ transgenic and wild-type mice were imaged using resting-state fMRI methods across their life-span in a cross-sectional design to analyze changes in FC in relation to the pathology. Transgenic mice show compromised development of FC during the first months of postnatal life compared with wild-type animals, resulting in functional impairments that affect in particular the sensory-motor cortex already in preplaque stage. These functional alterations were accompanied by structural changes as reflected by reduced fractional anisotropy values, as derived from diffusion tensor imaging. Our results suggest cerebral amyloidosis in mice is preceded by impairment of neuronal networks and white matter structures. FC analysis in mice is an attractive tool for studying the implications of impaired neuronal networks in models of cerebral amyloid pathology.
authors.affiliation: Institute for Biomedical Engineering, and Center for Neuroscience Research, University and ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Joanes
authors.initials: J
authors.lastname: Grandjean
authors.affiliation: Institute for Biomedical Engineering, and.
authors.forename: Aileen
authors.initials: A
authors.lastname: Schroeter
authors.affiliation: Department of Information Technology and Electrical Engineering, and.
authors.forename: Pan
authors.initials: P
authors.lastname: He
authors.affiliation: Seminar for Statistics, ETH Zurich, 8092 Zurich, Switzerland, and.
authors.forename: Matteo
authors.initials: M
authors.lastname: Tanadini
authors.affiliation: Institute of Pharmacology and Toxicology and.
authors.forename: Ruth
authors.initials: R
authors.lastname: Keist
authors.affiliation: Institute of Pharmacology and Toxicology and.
authors.forename: Dimitrije
authors.initials: D
authors.lastname: Krstic
authors.affiliation: Center for Neuroscience Research, University and ETH Zurich, 8093 Zurich, Switzerland, Division of Psychiatry Research, University of Zurich, 8008 Zurich, Switzerland.
authors.forename: Uwe
authors.initials: U
authors.lastname: Konietzko
authors.affiliation: Institute for Biomedical Engineering, and Center for Neuroscience Research, University and ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Jan
authors.initials: J
authors.lastname: Klohs
authors.affiliation: Center for Neuroscience Research, University and ETH Zurich, 8093 Zurich, Switzerland, Division of Psychiatry Research, University of Zurich, 8008 Zurich, Switzerland.
authors.forename: Roger M
authors.initials: RM
authors.lastname: Nitsch
authors.affiliation: Institute for Biomedical Engineering, and Center for Neuroscience Research, University and ETH Zurich, 8093 Zurich, Switzerland, Institute of Pharmacology and Toxicology and rudin@biomed.ee.ethz.ch.
authors.forename: Markus
authors.initials: M
authors.lastname: Rudin
mesh_terms: D000375:Aging / Q000502:physiology; D000544:Alzheimer Disease / Q000473:pathology; D000686:Amyloidosis / Q000235:genetics / Q000473:pathology*; D000818:Animals; D016880:Anisotropy; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009415:Nerve Net / Q000473:pathology; D009434:Neural Pathways / Q000502:physiology*; D066127:White Matter / Q000033:anatomy & histology* / Q000254:growth & development
keywords: ArcAβ; diffusion tensor imaging; fMRI; functional connectivity; mouse; resting state