In vivo visualization of Alzheimer's amyloid plaques by magnetic resonance imaging in transgenic mice without a contrast agent

One of the cardinal pathologic features of Alzheimer's disease (AD) is the formation of senile, or amyloid, plaques. Transgenic mice have been developed that express one or more of the genes responsible for familial AD in humans. Doubly transgenic mice develop “human‐like” plaques, providing a...

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Bibliographic Details
Published in:Magnetic resonance in medicine 2004-12, Vol.52 (6), p.1263-1271
Main Authors: Jack Jr, Clifford R., Garwood, Michael, Wengenack, Thomas M., Borowski, Bret, Curran, Geoffrey L., Lin, Joseph, Adriany, Gregor, Gröhn, Olli H. J., Grimm, Roger, Poduslo, Joseph F.
Format: Article
Language:English
Subjects:
Alzheimer Disease - pathology
Alzheimer's disease
Animals
Brain - pathology
magnetic resonance imaging
Magnetic Resonance Imaging - methods
Mice
Mice, Transgenic
MR microscopy
Plaque, Amyloid - pathology
transgenic mice
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Summary:One of the cardinal pathologic features of Alzheimer's disease (AD) is the formation of senile, or amyloid, plaques. Transgenic mice have been developed that express one or more of the genes responsible for familial AD in humans. Doubly transgenic mice develop “human‐like” plaques, providing a mechanism to study amyloid plaque biology in a controlled manner. Imaging of labeled plaques has been accomplished with other modalities, but only MRI has sufficient spatial and contrast resolution to visualize individual plaques noninvasively. Methods to optimize visualization of plaques in vivo in transgenic mice at 9.4 T using a spin echo sequence based on adiabatic pulses are described. Preliminary results indicate that a spin echo acquisition more accurately reflects plaque size, while a T2* weighted gradient echo sequence reflects plaque iron content, not plaque size. In vivo MRI–ex vivo MRI–in vitro histologic correlations are provided. Histologically verified plaques as small as 50 μm in diameter were visualized in living animals. To our knowledge this work represents the first demonstration of noninvasive in vivo visualization of individual AD plaques without the use of a contrast agent. Magn Reson Med 52:1263–1271, 2004. © 2004 Wiley‐Liss, Inc.
ISSN:0740-3194
1522-2594
DOI:10.1002/mrm.20266