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Neurobiol Aging. 2015 Feb;36(2):638-47. doi: 10.1016/j.neurobiolaging.2014.08.032. Epub 2014 Sep 6.

Altered brain development in an early-onset murine model of Alzheimer's disease.

Author information

1
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.
2
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.
3
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.
4
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.
5
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.

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.

KEYWORDS:

Brain development; Longitudinal magnetic resonance imaging; Mouse models of Alzheimer's disease; Neuroanatomy

[Indexed for MEDLINE]

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