A metabolomic study of the CRND8 transgenic mouse model of Alzheimer's disease.
Alzheimer's disease is the most common neurodegenerative disease of the central nervous system characterized by a progressive loss in memory and deterioration of cognitive functions. In this study the transgenic mouse TgCRND8, which encodes a mutant form of the amyloid precursor protein 695 with both the Swedish and Indiana mutations and develops extracellular amyloid beta-peptide deposits as early as 2-3 months, was investigated. Extract from eight brain regions (cortex, frontal cortex, cerebellum, hippocampus, olfactory bulb, pons, midbrain and striatum) were studied using (1)H NMR spectroscopy. Analysis of the NMR spectra discriminated control from APP695 tissues in hippocampus, cortex, frontal cortex, midbrain and cerebellum, with hippocampal and cortical region being most affected. The analysis of the corresponding loading plots for these brain regions indicated a decrease in N-acetyl-L-aspartate, glutamate, glutamine, taurine (exception hippocampus), gamma-amino butyric acid, choline and phosphocholine (combined resonances), creatine, phosphocreatine and succinate in hippocampus, cortex, frontal cortex (exception gamma-amino butyric acid) and midbrain of affected animals. An increase in lactate, aspartate, glycine (except in midbrain) and other amino acids including alanine (exception frontal cortex), leucine, iso-leucine, valine and water soluble free fatty acids (0.8-0.9 and 1.2-1.3 ppm) were observed in the TgCRND8 mice. Our findings demonstrate that the perturbations in metabolism are more widespread and include the cerebellum and midbrain. Furthermore, metabolic perturbations are associated with a wide range of metabolites which could improve the diagnosis and monitoring of the progression of Alzheimer's disease.
Salek
Reza M
RM
Department of Biochemistry, The Hopkins Building, Tennis Court Road, University of Cambridge, Cambridge CB21QW, UK.
Xia
Jing
J
Innes
Amy
A
Sweatman
Brian C
BC
Adalbert
Robert
R
Randle
Suzanne
S
McGowan
Eileen
E
Emson
Piers C
PC
Griffin
Julian L
JL
D000544:Alzheimer Disease / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D055442:Metabolome / Q000235:genetics; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic
D015415:Biomarkers