title: Gray and white matter degeneration revealed by diffusion in an Alzheimer mouse model.
abstract: In patients with Alzheimer's disease (AD) the severity of white matter degeneration correlates with the clinical symptoms of the disease. In this study, we performed diffusion-tensor magnetic resonance imaging at ultra-high field in a mouse model for AD (APP(swe)/PS1(dE9)) in combination with a voxel-based approach and tractography to detect changes in water diffusivity in white and gray matter, because these reflect structural alterations in neural tissue. We found substantial changes in water diffusion parallel and perpendicular to axonal tracts in several white matter regions like corpus callosum and fimbria of the hippocampus, that match with previous findings of axonal disconnection and myelin degradation in AD patients. Moreover, we found a significant increase in diffusivity in specific hippocampal subregions, which is supported by neuronal loss as visualized with Klüver-Barrera staining. This work demonstrates the potential of ultra-high field diffusion-tensor magnetic resonance imaging as a noninvasive modality to describe white and gray matter structural changes in mouse models for neurodegenerative disorders, and provides valuable knowledge to assess future AD prevention strategies in translational research.
authors.affiliation: Department of Anatomy, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Valerio
authors.initials: V
authors.lastname: Zerbi
authors.forename: Michiel
authors.initials: M
authors.lastname: Kleinnijenhuis
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Fang
authors.forename: Diane
authors.initials: D
authors.lastname: Jansen
authors.forename: Andor
authors.initials: A
authors.lastname: Veltien
authors.forename: Jack
authors.initials: J
authors.lastname: Van Asten
authors.forename: Nienke
authors.initials: N
authors.lastname: Timmer
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Dederen
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Kiliaan
authors.forename: Arend
authors.initials: A
authors.lastname: Heerschap
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009474:Neurons / Q000473:pathology*