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

Abstract

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 {beta}-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.

Authors:
; ; ; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
930613
Report Number(s):
BNL-80928-2008-JA
Journal ID: ISSN 0021-9258; JBCHA3; TRN: US200904%%812
DOE Contract Number:
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Biological Chemistry; Journal Volume: 281; Journal Issue: 1
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ANIMALS; BRAIN; CREATINE; DISEASES; ENERGY BALANCE; HIPPOCAMPUS; METABOLISM; MUTANTS; PATHOLOGY; PHOSPHOTRANSFERASES; PRECURSOR; PROTEINS; TRANSGENIC MICE; national synchrotron light source

Citation Formats

Gallant,M., Rak, M., Szeghalmi, A., Del Bigio, M., Westaway, D., Yang, J., Julian, R., and Gough, K. Focally Elevated Creatine Detected in Amyloid Precursor Protein (APP) Transgenic Mice and Alzheimer Disease Brain Tissue. United States: N. p., 2006. Web. doi:10.1074/jbc.C500244200.
Gallant,M., Rak, M., Szeghalmi, A., Del Bigio, M., Westaway, D., Yang, J., Julian, R., & Gough, K. Focally Elevated Creatine Detected in Amyloid Precursor Protein (APP) Transgenic Mice and Alzheimer Disease Brain Tissue. United States. doi:10.1074/jbc.C500244200.
Gallant,M., Rak, M., Szeghalmi, A., Del Bigio, M., Westaway, D., Yang, J., Julian, R., and Gough, K. Sun . "Focally Elevated Creatine Detected in Amyloid Precursor Protein (APP) Transgenic Mice and Alzheimer Disease Brain Tissue". United States. doi:10.1074/jbc.C500244200.
@article{osti_930613,
title = {Focally Elevated Creatine Detected in Amyloid Precursor Protein (APP) Transgenic Mice and Alzheimer Disease Brain Tissue},
author = {Gallant,M. and Rak, M. and Szeghalmi, A. and Del Bigio, M. and Westaway, D. and Yang, J. and Julian, R. and Gough, K.},
abstractNote = {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 {beta}-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.},
doi = {10.1074/jbc.C500244200},
journal = {Journal of Biological Chemistry},
number = 1,
volume = 281,
place = {United States},
year = {Sun Jan 01 00:00:00 EST 2006},
month = {Sun Jan 01 00:00:00 EST 2006}
}