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Journal of Biomedicine and Biotechnology
Volume 2006 (2006), Article ID 35936, 11 pages
Review Article

The Creatine Kinase/Creatine Connection to Alzheimer's Disease: CK Inactivation, APP-CK Complexes and Focal Creatine Deposits

1Institute of Cell Biology, ETH Zurich, Hönggerberg HPM, Zurich CH-8093, Switzerland
2INSERM E0221, Laboratory of Fundamental and Applied Bioenergetics, University Joseph Fourier, Grenoble, France
3Department of Neurology, University of Tennessee Health Science Center, Memphis, TN 38163, USA
4Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada R3T 2N2

Received 12 December 2005; Revised 28 February 2006; Accepted 28 February 2006

Copyright © 2006 Tanja S. Bürklen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Cytosolic brain-type creatine kinase (BB-CK), which is coexpressed with ubiquitous mitochondrial uMtCK, is significantly inactivated by oxidation, in Alzheimer's disease (AD) patients. Since CK has been shown to play a fundamental role in cellular energetics of the brain, any disturbance of this enzyme may exasperate the AD disease process. Mutations in amyloid precursor protein (APP) are associated with early onset AD and result in abnormal processing of APP, and accumulation of Aβ peptide, the main constituent of amyloid plaques in AD brain. Recent data on a direct interaction between APP and the precursor of uMtCK support an emerging relationship between AD, cellular energy levels and mitochondrial function. In addition, recently discovered creatine (Cr) deposits in the brain of transgenic AD mice, as well as in the hippocampus from AD patients, indicate a direct link between perturbed energy state, Cr metabolism and AD. Here, we review the roles of Cr and Cr-related enzymes and consider the potential value of supplementation with Cr, a potent neuroprotective substance. As a hypothesis, we consider whether Cr, if given at an early time point of the disease, may prevent or delay the course of AD-related neurodegeneration.