title: Altered brain development in an early-onset murine model of Alzheimer's disease.
abstract: Murine models of Alzheimer's disease (AD) have been used to draw associations between atrophy of neural tissue and underlying pathology. In this study, the early-onset TgCRND8 mouse model of AD and littermate controls were scanned longitudinally with in vivo manganese-enhanced MRI (MEMRI) before and after the onset of amyloid plaque deposition at 12 weeks of age. Separate cohorts of mice were scanned at 1 week (ex vivo imaging) and 4 weeks (MEMRI) of age to investigate early life alterations in the brain. Contrary to our expectations, differences in neuroanatomy were found in early post-natal life, preceding plaque deposition by as much as 11 weeks. Many of these differences remained at all imaging time points, suggesting that they were programmed early in life and were unaffected by the onset of pathology. Furthermore, rather than showing atrophy, many regions of the TgCRND8 brain grew at a faster rate compared to controls. These regions contained the greatest density of amyloid plaques and reactive astrocytes. Our findings suggest that pathological processes as well as an alteration in brain development influence the TgCRND8 neuroanatomy throughout the lifespan.
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, 25 Orde Street, M5T 3H7, Toronto, Ontario, Canada; Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Toronto, Ontario, Canada; Department of Medical Biophysics, Faculty of Medicine, University of Toronto, 7 floor, 610 University Ave, Toronto, ON, M5G 2M9, Toronto, Ontario, Canada. Electronic address: rylan.allemang-grand@mouseimaging.ca.
authors.forename: R
authors.initials: R
authors.lastname: Allemang-Grand
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, 25 Orde Street, M5T 3H7, Toronto, Ontario, Canada; Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Toronto, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Scholz
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, 25 Orde Street, M5T 3H7, Toronto, Ontario, Canada; Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Toronto, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Ellegood
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, 25 Orde Street, M5T 3H7, Toronto, Ontario, Canada; Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Toronto, Ontario, Canada.
authors.forename: L S
authors.initials: LS
authors.lastname: Cahill
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, 25 Orde Street, M5T 3H7, Toronto, Ontario, Canada; Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Toronto, Ontario, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Laliberté
authors.affiliation: Department of Medical Biophysics, Faculty of Medicine, University of Toronto, 7 floor, 610 University Ave, Toronto, ON, M5G 2M9, Toronto, Ontario, Canada; Tanz Centre for Research in Neurodegenerative Diseases, Krembil Discovery Tower, 60 Leonard Avenue, 4th floor, M5T 2S8, Toronto, Ontario, Canada.
authors.forename: P E
authors.initials: PE
authors.lastname: Fraser
authors.affiliation: Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Toronto, Ontario, Canada; Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Medical Sciences Building, 1 King's College Circle, Room 2374, M5S 1A8, Toronto, Ontario, Canada; Department of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Medical Sciences Building, M5S 1A8, Toronto, Ontario, Canada.
authors.forename: S A
authors.initials: SA
authors.lastname: Josselyn
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, 25 Orde Street, M5T 3H7, Toronto, Ontario, Canada; Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Toronto, Ontario, Canada; Department of Medical Biophysics, Faculty of Medicine, University of Toronto, 7 floor, 610 University Ave, Toronto, ON, M5G 2M9, Toronto, Ontario, Canada.
authors.forename: J G
authors.initials: JG
authors.lastname: Sled
authors.affiliation: Mouse Imaging Centre, Hospital for Sick Children, 25 Orde Street, M5T 3H7, Toronto, Ontario, Canada; Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Toronto, Ontario, Canada; Department of Medical Biophysics, Faculty of Medicine, University of Toronto, 7 floor, 610 University Ave, Toronto, ON, M5G 2M9, Toronto, Ontario, Canada.
authors.forename: J P
authors.initials: JP
authors.lastname: Lerch
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D001284:Atrophy; D001921:Brain / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D008279:Magnetic Resonance Imaging / Q000379:methods; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology
keywords: Brain development; Longitudinal magnetic resonance imaging; Mouse models of Alzheimer's disease; Neuroanatomy