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The Journal of Neuroscience, October 26, 2005, 25(43):10041-10048; doi:10.1523/JNEUROSCI.2588-05.2005

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Neurobiology of Disease
In Vivo Magnetic Resonance Microimaging of Individual Amyloid Plaques in Alzheimer's Transgenic Mice

Clifford R. Jack, Jr,¹ Thomas M. Wengenack,² Denise A. Reyes,¹ Michael Garwood,³ Geoffrey L. Curran,² Bret J. Borowski,¹ Joseph Lin,³ Gregory M. Preboske,¹ Silvina S. Holasek,² Gregor Adriany,³ and Joseph F. Poduslo²

¹Department of Radiology and ²Molecular Neurobiology Laboratory, Departments of Neurology, Neuroscience, and Biochemistry/Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, and ³Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical School, Minneapolis, Minnesota 55455

The ability to detect individual Alzheimer's amyloid plaques in vivo by magnetic resonance microimaging (MRI) should improve diagnosis and also accelerate discovery of effective therapeutic agents for Alzheimer's disease (AD). Here, we perform in vivo and ex vivo MRI on double transgenic AD mice as well as wild-type mice at varying ages and correlate these with thioflavin-S and iron staining histology. Quantitative counts of individual plaques on MRI increase with age and correlate with histologically determined plaque burden. Plaques 20 µm in diameter can be detected in AD mice as young as 3 months of age with ex vivo MRI. Plaques 35 µm in diameter can be detected by 9 months of age with in vivo MRI. In vivo MRI of individual Alzheimer's amyloid plaques provides a noninvasive estimate of plaque burden in transgenic AD mice that might be useful in assessing the efficacy of amyloid reduction therapies.

Key words: aging; amyloid; Alzheimer's disease; magnetic resonance microimaging; plaque; transgenic mice

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Received June 23, 2005; revised August 23, 2005; accepted September 20, 2005.

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