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Table 3
Summary of metabolomics studies conducted in AD human samples.
| Sample Size | Sample Source | Platform | Findings | Ref. |
|---|---|---|---|---|
| AD(n = 22) CN(n = 18) |
Serum | DIMS | ↓PUFA-PCs; ↑SFA-PCs |
(Gonzalez-Dominguez et al., 2012) |
| AD(n = 22) CN(n = 18) |
Serum | DIMS | ↓PUFA-PLs, valine, glutamine, N-acetyl-glutamine, glutamate, histidine, arginine, dopamine, carnitine, creatine; ↑SFA-PLs, free fatty acids, eicosanoids, triglycerides, choline, glycerophosphocholine, glucose |
(Gonzalez-Dominguez et al., 2014e) |
| AD(n = 22) CN(n = 18) |
Serum | DIMS | ↓PUFA-PLs, oleamide, histidine, arginine, imidazole, taurine, guanidine, putrescine; ↑eicosanoids, diglycerides, kynurenine |
(Gonzalez-Dominguez et al., 2014c) |
| AD(n = 19) CN(n = 17) |
Serum | DIMS | ↓PUFA-PLs, LPLs, plasmalogens; ↑SFA-PLs |
(Gonzalez-Dominguez et al., 2014b) |
| AD(n = 30) CN(n = 30) |
Serum | DIMS | ↓Fatty acid amides, urea, creatine, malate, taurine, dopamine, serotonin; ↑ceramides, diglycerides, free fatty acids, alanine, picolinic acid |
(Gonzalez-Dominguez et al., 2015a) |
| AD(n = 26) CN(n = 26) |
Plasma | DIMS | ↓Long-chain sphingomyelins; ↑ceramides |
(Han XL et al., 2011) |
| AD(n = 90) MCI(n = 77) CN(n = 51) |
Serum | DIMS | ↓Plasmalogens; ↑diglycerides |
(Wood et al., 2016) |
| AD(n = 43) MCI(n = 33) CN(n = 35) |
Plasma | DIMS | ↓Phosphatidylcholines; ↑lyso-phosphatidylcholines |
(Klavins et al., 2015) |
| AD(n = 23) CN(n = 21) |
Serum | GC-MS | ↓Valine, urea, aspartate, pyroglutamate, glutamine, phenylalanine, asparagine, ornithine, pipecolate, histidine, tyrosine, palmitic acid, urate, tryptophan, stearic acid, cysteine; ↑lactate, α-ketoglutarate, isocitrate, glucose, oleic acid, adenosine, cholesterol |
(Gonzalez-Dominguez et al., 2015b) |
| AD(n = 37 CN(n = 46) |
Serum | GC-MS | ↑Glutamate | (Orešič et al., 2018) |
| AD(n = 10) MCI(n = 10) CN(n = 10) |
Plasma | RP-MS | ↓Lysophospholipid (18:1) | (Sato et al., 2010) |
| AD(n = 10) CN(n = 10) |
Plasma | RP-MS | ↓Demosterol | (Sato et al., 2012) |
| AD(n = 16) MCI(n = 12) CN(n = 10) |
Plasma | RP-MS | ↑1-(9E-hexadecenoyl)-sn-glycero-3-phosphocholine, d-glucosaminide, glycocholic acid, glycodeoxycholic acid, glycochenodeoxycholic acid | (Greenberg et al., 2009) |
| AD(n = 20) CN(n = 20) |
Plasma | RP-MS | ↓Lysophosphatidylcholines, tryptophan, phytosphingosine, dihydrosphingosine, hexadecasphinganine | (Li et al., 2010a) |
| AD(n = 36) MCI(n = 48) CN(n = 40) |
Plasma | RP-MS | ↓Long chain cholesteryl esters | (Proitsi et al., 2015) |
| AD(n = 205) CN(n = 207) |
Plasma | RP-MS | ↓Phosphatidylcholines ↑Ceramide |
(Kim et al., 2016) |
| AD(n = 52) MCI(n = 62) CN(n = 59) |
Plasma | RP-MS | ↓Phosphatidylcholines | (Whiley et al., 2014) |
| AD/MCI(n = 35) Converters(n = 18) CN(n = 53) |
Plasma | RP-MS | ↓Phosphatidylcholines, lyso-phospholipids, serotonin, phenylalanine, proline, lysine, taurine, acyl-carnitines, malate; ↑glycoursodeoxycholic acid, proline-asparagine |
(Mapstone et al., 2014) |
| AD(n = 75) MCI(n = 17) CN(n = 45) |
Serum | RP-MS | ↓PUFA-PLs, PUFA-SMs, sulfatides, monoglycerides, oleamide, histidine pregnenolone sulfate; ↑SFA-PLs, SFA-SMs, ceramides, acyl-carnitines, phenyl-acetyl-glutamine |
(Raúl et al., 2016) |
| AD(n = 148) CN(n = 152) |
Plasma | RP-MS | ↓Cholesteryl esters, triglycerides; ↑phosphatidylcholine |
(Proitsi et al., 2017) |
| AD(n = 175) MCI(n = 356) CN(n = 189) |
Serum | RP-MS | ↓Acyl-carnitines, phosphatidylcholines, sphingomyelins; ↑valine, α-aminoadipic acid |
(Toledo et al., 2017) |
| AD(n = 660) MCI(n = 583) |
Serum | RP-MS | ↑Sphinganine-1-phosphate, 7-ketocholesterol, 3-methoxytyrosine, deoxyribose-5-phosphate, p-phenyllactic acid, lyso-phosphatidylcholine; ↓phenylalanine, ornithine, glutamate |
(Liang et al., 2016b) |
| AD(n = 46) CN(n = 37) |
Serum | RP-MS | ↓1-methylinosine, 16-bromo-9-hexadecenoic acid, lysophosphatidylcholines, dihydrosphingosine, N-acetyl-glutamine, 1α, 25-dihydroxy-2α-(3-hydroxypropoxy) vitamin D3; ↑palmitic amide, monoiodothyronine, antrimethyltridecanoic acid, PGE2α dimethyl amine, (6R)-vitamin D3 6, 19- (4-phenyl-1, 2, 4-triazoline-3, 5-dione) |
(Cui et al., 2014) |
| AD_MCI(n = 19) MCI(n = 16) CN(n = 37) |
Plasma | HILIC-MS | ↓4-amino-butanal, γ-aminobutyric acid, ornithine, N-acetyl-putrescine; ↑creatine, arginine, methylthioadenosine, N-acetyl-spermidine, N-diacetyl-spermine, putrescine, spermidine, spermine |
(Graham et al., 2015) |
| AD(n = 42) MCI(n = 14) CN(n = 37) |
Serum | CE-MS | ↓Creatine, asparagine, methionine, histidine, carnitine, N-acetyl-spermidine, valeryl-carnitine; ↑choline, creatinine, dimethylarginine, homocysteinyl-cysteine, acyl-carnitines, peptides |
(Gonzalez-Dominguez et al., 2014a) |
| AD(n = 47) MCI(n = 143) CN(n = 46) |
Serum | RP-MS/ GC-MS |
Baseline: ↓plasmalogens, phosphatidylcholines, sphingomyelins, sterols; ↑histamine Progression: ↑2, 4-dihydroxybutanoic acid |
(Orešič et al., 2011) |
| AD(n = 57) MCI(n = 58) CN(n = 57) |
Plasma | RP-MS/ GC-MS |
↓Fatty acids, dimethylglycine, glutamate, uridine, glyceraldehyde, butanedioic acid, 2-butenedioic acid, 5-oxoproline, taurine, hypotaurine, malate; ↑glutamine, 2-aminoadipic acid, proline, cysteine, cytidine, thymine, hypoxanthine, carbohydrates, citrate |
(Wang G et al., 2014) |
| AD(n = 30) MCI(n = 30) CN(n = 30) |
Plasma | RP-MS/ HILIC-MS |
↓Sphingomyelins | (Armirotti et al., 2014) |
| AD(n = 15) MCI(n = 15) CN(n = 15) |
Plasma | RP-MS/ HILIC-MS |
Changes in more than 150 metabolites (amino acids, energy-related metabolites, lipids, neurotransmitters) | (Trushina et al., 2013b) |
| AD(n = 3) FTD(n = 4) LBD(n = 3) CN(n = 9) |
Serum | CE-MS | ↑β-alanine, creatinine, hydroxyproline, glutamine, isocitrate, cytidine | (Tsuruoka et al., 2013) |
| AD(n = 12) CN(n = 5) |
Whole brain | MRS | ↓N-acetyl-aspartate, γ-aminobutyric acid; ↑ glutamate |
(Klunk et al., 1992) |
| AD(n = 13) CN(n = 4) |
Temporoparietal cortex | MRS | ↓N-acetyl-aspartate, creatine, γ-aminobutyric acid | (Mohanakrishnan et al., 1995) |
| AD(n = 13) CN(n = 4) |
Hippocampus, cerebellum | MRS | ↓N-acetyl-aspartate, γ-aminobutyric acid | (Mohanakrishnan et al., 1997) |
| AD(n = 8) ALS(n = 11) |
Frontal cortex | NMR | ↑Alanine, acetate, glutamate, glutamine; ↓lactate, creatine |
(Botosoa et al., 2012) |
| AD(n = 15) CN(n = 15) |
Neocortex | NMR | ↑Alanine, taurine | (Graham et al., 2014) |
| AD(n = 24) CN(n = 6) |
Superior frontal cortex, superior temporal cortex, inferior parietal cortex, cerebellum | DIMS | ↓Plasmalogens | (Han et al., 2001) |
| AD(n = 17) CN(n = 5) |
Middle frontal gyrus, superior temporal gyrus, inferior parietal lobule, hippocampus, subiculum, entorhinal cortex | DIMS | ↓Sulfatides; ↑ceramides |
(Han et al., 2002) |
| AD(n = 6) CN(n = 8) |
Superior frontal gyrus | DIMS | ↓Sulfatides | (Cheng et al., 2013) |
| AD(n = 34) MCI(n = 19) CN(n = 28) |
Frontal cortex grey matter, frontal cortex white matter | DIMS | ↓Plasmalogens, phosphatidylethanolamines, docosahexaenoic acid, phosphatidylethanolamines, sulfatides; ↑monoglycerides, diglycerides ; ↑monoglycerides, diglycerides, VLCFA 26:0 |
(Wood et al., 2015) |
| AD(n = 9) CN(n = 9) |
Hippocampus, entorhinal cortex, middle-temporal gyrus, sensory cortex, motor cortex, cingulate gyrus, cerebellum | GC-MS | Changes in 55 metabolites, including energy related metabolites (glucose metabolism, TCA), amino acids, nucleosides, and others | (Xu et al., 2016) |
| AD(n = 10) CN(n = 10) |
Frontal lobe, parietal lobe, occipital lobe | RP-MS | ↑Spermidine, spermine, N-acetyl-spermidine, N-acetyl-spermine, putrescine | (Inoue et al., 2013) |
| ADI–II(n = 7) ADIII–IV(n = 4) ADV–VI(n = 5) CN(n = 4) |
Entorhinal cortex | RP-MS | ↓dGMP, glycine, xanthosine, inosine diphosphate, deoxyguanosine; ↑guanine |
(Ansoleaga et al., 2015) |
| AD(n = 15) CN(n = 15) |
Neocortex | HILIC-MS | Seventy-six unidentified discriminant signals | (Graham et al., 2013a) |
| AD(n = 21) CN(n = 19) |
Frontal cortex | RP-MS/ HILIC-MS |
Alterations in the metabolism of phospholipids and six metabolic pathways of the central metabolism: Alanine, Aspartate, and Glutamate Metabolism; Arginine and Proline Metabolism; Cysteine and Methionine Metabolism; Glycine, Serine, and Threonine Metabolism; Purine Metabolism; Pantothenate and CoA Biosynthesis | (Paglia et al., 2016) |
| AD(n = 14) asyAD(n = 15) CN(n = 14) |
Middle frontal gyrus Inferior temporal gyrus Cerebellum |
RP-MS | ↓Glucose | (An et al., 2017) |
| AD(n = 14) asyAD(n = 15) CN(n = 14) |
Middle frontal gyrus Inferior temporal Gyrus Cerebellum |
GC-MS | ↑Cholestenol, docosahexaenoic acid, carbamic acid, hexanedioic acid, ascorbate, gluconic acid, cysteine, L-DOPA, allantoin, coumaric acid, adenine, deoxyflurouridine, arginine, GABA; ↓cholesterol, linoleic acid, methyl-heptadecadiynoic acid, oleic acid, palmitic acid, dimethylglycine, guanidobutanoate, aminobutanal, aspartate, fumaric acid, linolenic acid, indoleacetic acid, eicosapentaenoic acid, hypoxanthine, oxoarginine, methyl-stearate, octadecanal |
(Snowden et al., 2017) |
| AD(n = 15) CN(n = 15) |
Post-mortem CSF | LCECA | ↓Norepinephrine, α-tocopherols, 3-methoxytyramine, ascorbate; ↑5-hydroxytryptophan, methoxy-hydroxyphenyl glycol |
(Kaddurah-Daouk et al., 2011) |
| AD(n = 34) MCI(n = 19) CN(n = 28) |
CSF | MS | CSF: ↓docosahexaenoic | (Wood et al., 2015) |
| AD(n = 20) CN(n = 27) |
CSF | NMR | Specific resonances in AD (unidentified) | (Kork et al., 2009) |
| AD(n = 10) CN(n = 34) |
CSF | NMR | ↑Creatinine | (Jukarainen et al., 2008) |
| AD(n = 76) early_AD(n = 26) MCI(n = 33) CN(n = 45) |
CSF | NMR | Phenylalanine, glutamate, lactate, acetate, α-hydroxyisovalerate, α-hydroxybutyrate | (Laakso et al., 2015) |
| AD(n = 50) CN(n = 50) |
CSF | DIMS | ↑Sphingomyelins, phosphatidylcholines | (Koal et al., 2015) |
| AD(n = 17) CN(n = 17) |
CSF | RP-MS | Fifty-three unidentified discriminant signals | (Myint et al., 2009) |
| AD(n = 40) MCI(n = 36) CN(n = 38) |
CSF | RP-MS | ↑Methionine, 5-hydroxyindoleacetic acid, vanillylmandelic acid, xanthosine, glutathione, hypoxanthine | (Kaddurah-Daouk et al., 2013) |
| AD(n = 23) AD_MCI(n = 9) sMCI(n = 22) CN(n = 19) |
CSF | CE-MS | ↓Arginine, suberylglycine, carnitine, histidine; ↑choline, valine, tripeptide, dimethylarginine, creatine, serine |
(Ibanez et al., 2012) |
| AD(n = 79) CN(n = 51) |
CSF | RP-MS/ GC-MS |
↓Uridine; ↑cysteine, tyrosine, phenylalanine, methionine, serine, pyruvate, taurine, creatinine, cortisol, dopamine |
(Czech et al., 2012) |
| AD(n = 40) CN(n = 38) |
CSF | RP-MS/ GC-MS |
Two unidentified discriminant signals | (Motsinger-Reif et al., 2013) |
| AD(n = 21), cMCI(n = 12) sMCI(n = 21) CN(n = 21) |
CSF | RP-MS/ HILIC-MS |
Changes in levels of uracil, xanthine, uridine, tyrosyl-serine, methylsalsolinol, nonanoylglycine, dopamine-quinone, caproic acid, vanylglycol, histidine, pipecolic acid, hydroxyphophinyl-piruvate, creatinine, taurine, C16-sphingosine-1-phosphate, tryptophan, 5′-methylthioadenosine | (Ibanez et al., 2013) |
| AD(n = 15) MCI(n = 15) CN(n = 15) |
CSF | RP-MS/ HILIC-MS |
Changes in more than 150 metabolites (amino acids, energy-related metabolites, lipids, neurotransmitters) | (Trushina et al., 2013a) |
| AD(n = 256) CN(n = 218) |
Saliva | RP-MS | ↓Inosine, 3-dehydrocarnitine, hypoxanthine; ↑sphinganine-1-phosphate, ornithine, p-phenyllactic acid |
(Liang et al., 2015) |
| AD(n = 660) MCI(n = 583) |
Saliva | RP-MS | ↓Inosine, 3-dehydrocarnitine, hypoxanthine; ↑cytidine, sphinganine-1-phosphate, ornithine, p-phenyllactic acid, pyroglutamate, glutamate, tryptophan |
(Liang et al., 2016a) |
| MCI(n = 20) CN(n = 20) |
Saliva | RP-MS | ↓Taurine, peptides, 1, 8-diazacyclotetradecane-2, 9-dione, 4-(hydroxylamino)-N, N-dimethylaniline; ↑2-amino-heptanoic acid/l-alanine-n-butyl ester/N-methyl-isoleucine |
(Zheng et al., 2012) |
| AD(n = 3) FTD(n = 4) LBD(n = 3) CN(n = 9) |
Saliva | CE-MS | ↓Arginine, tyrosine | (Tsuruoka et al., 2013) |
| AD(n = 46) CN(n = 37) |
Urine | RP-MS | ↓Acetyl-carnitine, estra-1, 3, 5(10), 7-tetraene-3, 17α-diol, p-cresol glucuronide, etiocholanolone glucuronide ; ↑N-acryloylglycine, argininosuccinic acid, dethiobiotin, isobutyryl-l-carnitine, 2-hydroxy-N-(2-hydroxyethyl)-N, N-dimethyl-1-dodecanaminium, l-aspartyl-4-phosphate, l-glutamine, 5-l-glutamylglycine, azelaic acid, aminopterin, cytidine |
(Cui et al., 2014) |
| AD(n = 31) MCI(n = 15) CN(n = 36) |
Hair | GC-MS | ↑7β-hydroxycholesterol | (Son et al., 2016) |
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