Neurochemical and cognitive changes precede structural abnormalities in the TgF344-AD rat model of Alzheimer’s disease
Caitlin F Fowler1,2, Dana Goerzen2, Gabriel A Devenyi2,3, Dan Madularu4, M Mallar F Chakravarty1,2,3, and Jamie Near2,5
1Biological and Biomedical Engineering, McGill University, Montreal, QC, Canada, 2Cerebral Imaging Centre, Douglas Mental Health University Institute, Verdun, QC, Canada, 3Psychiatry, McGill University, Montreal, QC, Canada, 4Center for Translational Neuroimaging, Northeastern University, Boston, MA, United States, 5Physical Studies Research Platform, Sunnybrook Research Institute, Toronto, ON, Canada
Alzheimer’s disease is a progressive neurodegenerative disorder with a decades-long pre-symptomatic phase, substantiating the need for prodromal biomarker development and early intervention. We employed longitudinal magnetic resonance imaging and spectroscopy in conjunction with behavioural testing to characterize the chronological order of appearance and progression of multiple facets of disease pathology in the TgF344-AD rat model. The TgF344-AD rat demonstrated impaired spatial reference memory by 4 months of age, followed by neurochemical abnormalities by 10 months and major structural changes by 16 months, most of which recapitulated documented changes in brain structure and tissue chemistry in human Alzheimer’s disease patients.
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