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Magnetic Resonance Imaging of Alzheimer's Pathology in the Brains of Living Transgenic Mice: A New Tool in Alzheimer's Disease Research

Mayo Clinic College of Medicine, Rochester, Minnesota; Mayo Clinic, Department of Radiology, 200 First Street SW, Rochester, MN 55905 jack.clifford{at}mayo.edu

Malgorzata Marjanska

Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical School, Minneapolis, Minnesota

Thomas M. Wengenack

Denise A. Reyes

Geoffrey L. Curran

Mayo Clinic College of Medicine, Rochester, Minnesota

Joseph Lin

Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical School, Minneapolis, Minnesota

Gregory M. Preboske

Joseph F. Poduslo

Mayo Clinic College of Medicine, Rochester, Minnesota

Michael Garwood

Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical School, Minneapolis, Minnesota

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Cardinal pathologic features of AD are amyloid plaques and neurofibrillary tangles, and most in the field believe that the initiating events ultimately leading to clinical AD center on disordered metabolism of amyloid beta protein. Mouse models of AD have been created by inserting one or more human mutations associated with disordered amyloid metabolism and that cause early onset familial AD into the mouse genome. Human-like amyloid plaque formation increases dramatically with age in these transgenic mice. Amyloid reduction in humans is a major therapeutic objective, and AD transgenic mice allow controlled study of this biology. Recent work has shown that amyloid plaques as small as 35 µm can be detected using in vivo magnetic resonance microimaging (MRMI) at high magnetic field (9.4 T). In addition, age-dependent changes in metabolite concentration analogous to those that have been identified in human AD patients can be detected in these transgenic mice using single-voxel ¹H magnetic resonance spectroscopy (¹H MRS) at high magnetic field. These MR-based techniques provide a new set of tools to the scientific community engaged in studying the biology of AD in transgenic models of the disease. For example, an obvious application is evaluating therapeutic modification of disease progression. Toward the end of this review, the authors include results from a pilot study demonstrating feasibility of using MRMI to detect therapeutic modification of plaque progression in AD transgenic mice.

Key Words: Magnetic resonance microimaging • 1H magnetic resonance spectroscopy • Alzheimer's disease • Alzheimer's disease therapy • Transgenic Alzheimer's mice

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