Focally elevated creatine detected in amyloid precursor protein (APP) transgenic mice and Alzheimer disease brain tissue.
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.
Gallant
Meghan
M
Department of Chemistry, University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada.
Rak
Margaret
M
Szeghalmi
Adriana
A
Del Bigio
Marc R
MR
Westaway
David
D
Yang
Jin
J
Julian
Robert
R
Gough
Kathleen M
KM
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D003401:Creatine / Q000737:chemistry / Q000378:metabolism*; D003460:Crystallization; D004734:Energy Metabolism / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D016612:Paraffin Embedding; D013055:Spectrophotometry, Infrared
D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D003401:Creatine