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Table 2
Summary of metabolomics studies conducted in animal models of AD.
| Animal model | Sample | Platform | Findings | Ref. |
|---|---|---|---|---|
| APPTg2576(n = 9) WT(n = 10) |
Frontal cortex | NMR | ↑Taurine; ↓N-acetyl-aspartate, glutamate, glutathione |
(Dedeoglu et al., 2004) |
| APPxPS1(n = 7–8) WT(n = 5–9) |
Whole brain | NMR | ↑Myo-inositol, choline, glycerophosphocholine; ↓succinate |
(Forster et al., 2012) |
| CRND8 (n = 5/5 young/old) WT (n = 4/8 young/old) |
Cortex, frontal cortex, cerebellum, hippocampus, striatum, pons, midbrain, olfactory bulb | NMR | ↑Lactate, aspartate, glycine, alanine, leucine, isoleucine, valine, free fatty acids; ↓N-acetyl-aspartate, glutamate, glutamine, taurine, γ-aminobutyric acid, choline, phosphocholine, creatine, phosphocreatine, succinate |
(Salek et al., 2010) |
| APP × PS1(n = 10) WT(n = 10) |
Cortex(frontal, occipital, parietal, temporal), thalamus, hippocampus | NMR | ↑Myo-inositol, scyllo-inositol; ↓N-acetyl-aspartate |
(Woo et al., 2010) |
| APPTg2576(n = 39) WT(n = 44) |
Frontal cortex, rhinal cortex, hippocampus, cerebellum, midbrain | NMR | ↑Creatine, taurine; ↓glutamate, N-acetyl-aspartate, myo-inositol, phosphocholine, γ-aminobutyric acid |
(Lalande et al., 2014) |
| APP × PS1(n = 6) WT(n = 6) |
Whole brain | NMR | ↓N-acetyl-aspartata, γ-aminobutyric acid, creatine, ascorbic acid | (Graham et al., 2013b) |
| APP × PS1(n = 6) WT(n = 6) |
Plasma | NMR | ↓Glutamate, glutamine, methionine, acetate, citrate | (Graham et al., 2013b) |
| APP × PS1(n = 27) WT(n = 33) |
Plasma | NMR | ↑Lipoproteins, triglycerides | (Wu et al., 2016) |
| APP × PS1(n = 27) WT(n = 33) |
Liver | NMR | ↑Unsaturated fatty acids, 3-hydroxybutyrate, aspartate, glutamine, uridine diphosphate, uridine monophosphate, adenosine monophosphate; ↓alanine, lactate, betaine | (Wu et al., 2016) |
| SAMP8(n = 5) SAMR1(n = 5) |
Serum | NMR | ↑Lactate, saturated fatty acids, alanine, methionine, glutamine, VLDL; ↓inosine, glucose, polyunsaturated fatty acids, choline, phosphocholine, HDL, LDL, 3-hydroxy-butyrate, citrate, pyruvate |
(Liang et al., 2008) |
| APPTg2576(n = 3–5) WT(n = 3–5) |
Urine | NMR | ↑3-hydroxykynurenine, homogentisate, allantoin, acetate, trans-aconitate, tyrosine, hippurate, citrate, urea; ↓trigonelline, 2-oxoglutarate, dimethylamine, trimethylamine, threonine, 1-methylnicotinamide |
(Fukuhara et al., 2013) |
| APPV717F, APPV717F × APOE APPsw APPsw × APOE WT |
Cortex, cerebellum | MS | ↓Sulfatides | (Cheng et al., 2010) |
| APP × PS1(n = 30) WT(n = 30) |
Serum | MS | ↑SFA-PLs, eicosanoids, triglycerides, diglycerides, choline, GPE, inosine; ↓PUFA-PLs, LPLs, cholesteryl esters, free fatty acids, urea, serine, valine, threonine, pyroglutamate, creatine, phosphoethanolamine, histidine, carnitine, glucose, tyrosine, tryptophan |
(Gonzalez-Dominguez et al., 2015c) |
| APP × PS1(n = 30) WT(n = 30) |
Hippocampus, cortex, cerebellum, olfactory bulb | MS | ↑LPLs, PL(18:0/20:4), 22:5PLs, 22:4-PLs, propionyl-carnitine, free fatty acids, eicosanoids, uracil, hypoxanthine, xanthine, FAPy-adenine, adenosine, inosine, acetate, propionate, pyruvate, alanine, choline, valine, G3P, phosphocholine, N-acetyl-spermidine, GPC, GPI; ↓PUFA-PLs, acyl-carnitines, steroids, adenine, UMP, AMP, urea, aspartate, dopamine, tyrosine, homocarnosine |
(Gonzalez-Dominguez et al., 2015h) |
| APP × PS1(n = 30) WT(n = 30) |
Liver, kidney, spleen, thymus | MS | Alterations in the metabolism of phospholipids, fatty acids, acyl-carnitines, eicosanoids, acyl-glycerols, steroids, amino acids, nucleotides, energy-related metabolites(changes depending on the tissue) | (Gonzalez-Dominguez et al., 2015e) |
| APP × PS1(n = 8–9) WT(n = 8–9) |
Brain, plasma | MS | Longitudinal perturbations(6–18 months) in metabolism of phospholipids, amino acids, polyamines and acyl-carnitines | (Pan et al., 2016) |
| APP × PS1 × IL4 (n = 7) APP × PS1(n = 7) WT(n = 7) |
Serum | MS | ↓Urea, histamine, threonine, aspartate, urocanic acid, dopamine, citrulline, tyrosine; ↑1-methyl-histamine, eicosanoids |
(Gonzalez-Dominguez et al., 2015g) |
| CRND8(n = 6) WT(n = 6) |
Hippocampus | MS | Alterations in the homeostasis of arachidonic acid, glucose metabolism and fatty acid β-oxidation | (Lin et al., 2013) |
| CRND8(n = 6) WT(n = 6) |
Cerebellum | MS | ↑Eicosanoids, amino acids and derivatives, xanthosine, xanthine, urate; ↓inosine, guanosine |
(Lin et al., 2014) |
| SAMP8 n = 5 (2 months) n = 6 (7 months) n = 7 (12 months) |
Hippocampus | GC-MS | ↑Cholesterol, oleic acid, phosphoglyceride, N-acetyl-aspartate; ↓alanine, serine, glycine, aspartate, glutamate, γ-aminobutyric acid, malic acid, butanedioic acid, fumaric acid, citric acid, pyroglutamic acid, urea, lactic acid |
(Wang HL et al., 2014) |
| TASTPM(n = 16) WT(n = 5) |
Whole brain | GC-MS | ↑D-fructose, valine, serine, threonine; ↑zymosterol |
(Hu et al., 2012) |
| TASTPM(n = 16) WT(n = 5) |
Plasma | GC-MS | ↑D-glucose, d-galactose, linoleica cid, arachidonic acid, palmitic acid, gluconic acid | (Hu et al., 2012) |
| APPTg2576(n = 15) WT(n = 17); CRND8(n = 9) WT(n = 9); APPV717I(n = 10) WT(n = 12) |
Urine | GC-MS | ↑Phenylacetone; ↓3-methylcyclopentanone, 4-methyl-6-hepten-3-one, 6-hydroxy-6-methyl-3-heptanone |
(Kimball et al., 2016b) |
| CRND8(n = 12) WT(n = 12) |
Urine | RP-MS | ↑Methionine, desaminotyrosine, phenylacetylglycine, dihydrouracil, ureidopropionic acid, thiocysteine; ↓choline, taurine, N1-acetyl-spermidine, 5-hydroxy-indoleacetic acid, hydroxyphenylglycine |
(Peng et al., 2014) |
| CRND8 (n = 18/12,12/18 weeks) WT(n = 12/12, 12/18 weeks) |
Urine | HILIC-MS | Fifty-five differential metabolites involved in the homeostasis of amino acids(e.g. tryptophan, tyrosine, phenylalanine, lysine), fatty acids, purines and pyrimidines, ascorbate, and others | (Tang et al., 2016) |
| APP × PS1(n = 30) WT(n = 30) |
Serum | RP-MS/ GC-MS |
Alterations in the metabolism of phospholipids, sphingolipids, fatty acids, cholesterol and bile acids, energy-related metabolites and amino acids | (Gonzalez-Dominguez et al., 2015d) |
| APP × PS1(n = 30) WT(n = 30) |
Hippocampus, cortex, striatum, cerebellum, olfactory bulb | RP-MS/ GC-MS |
Alterations in the metabolism of phospholipids, sphingolipids, energy-related metabolites, amino acids and nucleotides | (Gonzalez-Dominguez et al., 2014d) |
| APP × PS1(n = 30) WT(n = 30) |
Liver, kidney | RP-MS/ GC-MS |
Alterations in the metabolism of phospholipids, sphingolipids, fatty acids, acyl-carnitines, cholesterol and bile acids, energy-related metabolites and amino acids | (Gonzalez-Dominguez et al., 2015f) |
| APP × PS1(n = 30) WT(n = 30) |
Spleen, thymus | RP-MS/ GC-MS |
Alterations in the metabolism of phospholipids, sphingolipids, fatty acids, acyl-carnitines, energy-related metabolites, amino acids and purines | (Gonzalez-Dominguez et al., 2015i) |
| APPTg2576(n = 3) PS1(n = 3) APP × PS1(n = 6) WT(n = 6) |
Hippocampus | RP-MS/ GC-MS |
Alterations in nucleotide, TCA cycle, energy transfer, carbohydrate, neurotransmitter and amino acid metabolic pathways | (Trushina et al., 2012) |
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