title: Complex interplay between brain function and structure during cerebral amyloidosis in APP transgenic mouse strains revealed by multi-parametric MRI comparison.
abstract: Alzheimer's disease is a fatal neurodegenerative disorder affecting the aging population. Neuroimaging methods, in particular magnetic resonance imaging (MRI), have helped reveal alterations in the brain structure, metabolism, and function of patients and in groups at risk of developing AD, yet the nature of these alterations is poorly understood. Neuroimaging in mice is attractive for investigating mechanisms underlying functional and structural changes associated with AD pathology. Several preclinical murine models of AD have been generated based on transgenic insertion of human mutated APP genes. Depending on the specific mutations, mouse strains express different aspects of amyloid pathology, e.g. intracellular amyloid-β (Aβ) aggregates, parenchymal plaques, or cerebral amyloid angiopathy. We have applied multi-parametric MRI in three transgenic mouse lines to compare changes in brain function with resting-state fMRI and structure with diffusion tensor imaging and high resolution anatomical imaging. E22ΔAβ developing intracellular Aβ aggregates did not present functional or structural alterations compared to their wild-type littermates. PSAPP mice displaying parenchymal amyloid plaques displayed mild functional changes within the supplementary and barrel field cortices, and increased isocortical volume relative to controls. Extensive reduction in functional connectivity in the sensory-motor cortices and within the default mode network, as well as local volume increase in the midbrain relative to wild-type have been observed in ArcAβ mice bearing intracellular Aβ aggregates as well as parenchymal and vascular amyloid deposits. Patterns of functional and structural changes appear to be strain-specific and not directly related to amyloid deposition.
authors.affiliation: Institute for Biomedical Engineering, University and ETH Zürich, Zürich, Switzerland.
authors.forename: Joanes
authors.initials: J
authors.lastname: Grandjean
authors.affiliation: Center for Neuroscience Research, University and ETH Zürich, Zürich, Switzerland; Division of Psychiatry Research, University of Zürich, Zürich, Switzerland.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Derungs
authors.affiliation: Center for Neuroscience Research, University and ETH Zürich, Zürich, Switzerland; Division of Psychiatry Research, University of Zürich, Zürich, Switzerland.
authors.forename: Luka
authors.initials: L
authors.lastname: Kulic
authors.affiliation: Center for Neuroscience Research, University and ETH Zürich, Zürich, Switzerland; Division of Psychiatry Research, University of Zürich, Zürich, Switzerland.
authors.forename: Tobias
authors.initials: T
authors.lastname: Welt
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, Toronto, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Henkelman
authors.affiliation: Center for Neuroscience Research, University and ETH Zürich, Zürich, Switzerland; Division of Psychiatry Research, University of Zürich, Zürich, Switzerland.
authors.forename: Roger M
authors.initials: RM
authors.lastname: Nitsch
authors.affiliation: Institute for Biomedical Engineering, University and ETH Zürich, Zürich, Switzerland; Center for Neuroscience Research, University and ETH Zürich, Zürich, Switzerland; Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland. Electronic address: rudin@biomed.ee.ethz.ch.
authors.forename: Markus
authors.initials: M
authors.lastname: Rudin
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000686:Amyloidosis / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D064847:Multimodal Imaging / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D016564:Amyloid beta-Protein Precursor
keywords: APP; Alzheimer's disease; Amyloid; MRI; Mouse; Resting-state