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J. Biol. Chem., Vol. 281, Issue 1, 5-8, January 6, 2006

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Focally Elevated Creatine Detected in Amyloid Precursor Protein (APP) Transgenic Mice and Alzheimer Disease Brain Tissue^*

Meghan Gallant12, Margaret Rak13, Adriana Szeghalmi, Marc R. Del Bigio4, David Westaway¶||, Jin Yang¶, Robert Julian**, and Kathleen M. Gough5

From the Department of Chemistry, University of Manitoba, Winnipeg, Manitoba R3T 2N2, the Department of Pathology, University of Manitoba, Winnipeg, Manitoba R3E 0W3, the ^¶Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2, the ^||Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 1L5, and the ^**Synchrotron Radiation Center, University of Wisconsin at Madison, Stoughton, Wisconsin 53589

The creatine/phosphocreatine system, regulated by creatine kinase, plays an important role in maintaining energy balance in the brain. Energy metabolism and the function of creatine kinase are known to be affected in Alzheimer diseased brain and in cells exposed to the -amyloid peptide. We used infrared microspectroscopy to examine hippocampal, cortical, and caudal tissue from 21–89-week-old transgenic mice expressing doubly mutant (K670N/M671L and V717F) amyloid precursor protein and displaying robust pathology from an early age. Microcrystalline deposits of creatine, suggestive of perturbed energetic status, were detected by infrared microspectroscopy in all animals with advanced plaque pathology. Relatively large creatine deposits were also found in hippocampal sections from post-mortem Alzheimer diseased human brain, compared with hippocampus from non-demented brain. We therefore speculate that this molecule is a marker of the disease process.

Received for publication, June 9, 2005 , and in revised form, October 13, 2005.

^* This work was supported by the Canadian Institutes of Health Research, the Manitoba Health Research Council (MHRC), and the Natural Sciences and Engineering Research Council (NSERC) Canada. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Co-first authors.

² Supported through an MHRC fellowship.

³ Supported through an NSERC PGS-A scholarship, a University of Manitoba graduate fellowship, and the McCrorie-West Family Fellowship for Alzheimer Research.

⁴ Dr. Del Bigio holds the Canada Research Chair in Developmental Neuropathology.

⁵ To whom correspondence should be addressed: Dept. of Chemistry, University of Manitoba, 350 Parker Bldg., Winnipeg, Manitoba R3T 2N2, Canada. Tel.: 204-474-6262; Fax: 204-474-7608; E-mail: kmgough{at}ms.umanitoba.ca.

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