Skip to main content
. 2018 Jan 12;8:719. doi: 10.3389/fneur.2017.00719

Table 4.

Application of metabolomics in samples from AD mouse models.

Analytical platform Samples Findings Reference
DIMS Brains and plasma from APP/PS1 and WT mice
  • APP/PS1 cortex and hippocampus had altered phospholipids and ACs

  • APP/PS1 blood serum had significant alterations in eicosanoids (LB4, HEPE, and prostaglandins)

  • Studies suggest altered lipid metabolism and energy utilization in APP/PS1 mice

(128, 129)

Absolute IDQ p180 Kit measured by UPLC-MS Longitudinal collection (6–18 months) of APP/PS1 and WT mouse brains and plasma
  • 6 months: ↑ Arg in brain, ↓ Gln and Pro in plasma

  • At 6–10 months: ↑ polyamines putrescine, spermidine, and spermine in brain and plasma

  • 10–12 months: ↓ Thr

  • 12 months: ↓ Gln and citrulline in plasma

  • Potential temporal disturbance in amino acids and lipid metabolism

(130)

Bile acid kit measured by LC-MS/MS Plasma and whole brain tissue from 5 APP/PS1 at 6 and 12 months of age
Plasma and neocortex from 10 AD and CN patients
  • Bile acids are perturbed in AD samples

  • Human plasma had ↓ CA in AD patients

  • APP/PS1 mouse plasma had ↑ CA at 6 months and ↓ hyodeoxycholic acid at 12 months

  • Human neocortex had ↓ taurocholic acid

  • APP/PS1 brain tissue: 6 months had ↑ lithocholic acid and ↓ TMCA; 12 months had ↓ TMCA, CA, β-muricholic acid, Ω-muricholic acid, taurocholic acid, and tauroursodeoxycholic acid

(131)

UHPLC-MS Urine from 30 APP/PS1 and CN mice at 2 months of age
  • Identification of potential early biomarkers in urine

  • ↑ Spermic acid, 2,4-guanidinobutanoic acid, nicotinuric acid, l-isoleucyl-l-proline, l-2,3-dihydrodipicolinate, 3,4-dihydroxyphenylglycol o-sulfate, N-acetyl-l-tyrosine, 5-hydroxyindoleacetic acid, 3-methoxybenzenepropanoic acid, and 3,4-dimethoxyphenylacetic acid

  • Dimethylarginine, 1-methyladenosine, citric acid, 5′-deoxyadenosine, 1-(beta-d-ribofuranosyl)-1,4-dihydronicotinamide, 7-methylinosine, 2-keto-6-acetamidocaproate, 7-aminomethyl-7-carbaguanine, succinyladenosine, benzaldehyde, urothion, 6-hydroxy-5-methoxyindole glucuronide, monobutyl phthalate, and tetrahydrocortisol

  • Had greatest impact on glyoxylate and dicarboxylate metabolism

(132)

Head-space GC-MS Urine of 15 APP mice, 15 Tg2576 mice, 9 TgCRND8 mice, and 10 APPLd2 mice and NTG littermates
  • ↑ Phenylacetone across all three APP mice

  • Linear discriminant analysis predicted groups with <16% error

  • Predictive metabolites include 6-hydroxy-6-methyl-3-heptanone, 3-methylcyclopentanone, 4-methyl-6-hepten-3-one, 1-octen-3-ol, 2-sec-butyl-4,5-dihydrothiazole, acetophenone, phenylacetone, o-toluidine

(133)

LC-MS and GC-MS Cortex and plasma from symptomatic APP/PS1 mice
  • CAD-31 was found to be neuroprotective

  • CAD-31 in plasma of APP/PS1 mice ↑ sphingolipids (glycosyl-N-stearoyl-sphingosine and sphingosine-1-phosphate)

  • CAD-31 in cortex of APP/PS1 mice ↑ monoacylglycerols (1-palmitoylglycerol, 2-palmitoylglycerol, 2-oleoylglycerol)

  • CAD-31 in plasma of control mice ↓ long-chain fatty acids (margarate, pentadecanoate, 10-nonadoconoate), ↑ acylcarnitines (C0, C16, C18:1), ↑ ketone body 3-hydroxybutyrate, ↑ sphingolipids (glycosyl-N-stearoyl-sphingosine, sphinganine-1-phosphate, sphingosine-1-phosphate, sphinganine)

  • CAD-31 in cortex of control mice was similar to plasma

(134)

HPLC-QTOF-MS Plasma from AD-induced mice (via Aβ42 injection) and controls (n = 8 per group)
  • Breviscapine treatment was neuroprotective in Aβ injected mice

  • Multivariate analysis of breviscapine treated Aβ mice identified indoleacrylic acid, C16 sphinganine, LPE (22:6), sulfolithocholic acid, LPC (16:0), PA (22:1/0:0), taurodeoxycholic acid, and PC (0:0/18:0)

  • Phospholipid and cholesterol modulation may be neuroprotective

(135)

IC-MS/MS Primary astrocytes of 5xFAD mice from neocorticies of 1- to 3-day-old mice
  • Pantethine has anti-inflammatory properties

  • AD astrocytes treated with pantethine had improved glycolytic and TCA cycle flux

  • Pantethine treatment in AD astrocytes augmented glucose-6-phosphate, glycerol-3-phosphate, αKG, fumarate, and succinate levels

(136)

EIS-MS/MS BMDMs derived from Trem2−/− and WT mice
  • ↓ UDP-glucose, CDP-ethanolamine, glucose-6-phosphate, fructose bisphosphate, citrate, and succinate

  • ↑ Indolacetate, glycerol-3-phosphate, malate, and fumarate

  • TREM2 deficiency perturbs mTOR signaling and nucleotide, glycolytic, and TCA cycle metabolites

  • Cyclone creatine supplement alleviates TREM2 deficiency in BMDMs

(137)

αKG, αketoglutarate; AD, Alzheimer’s disease; Arg, arginine; APP, amyloid precursor protein; BMDMs, bone marrow-derived macrophages; CA, cholic acid; CDP, cytidine diphosphate; CN, control; DIMS, direct infusion mass spectrometry; EIS-MS/MS, electrospray ionization; FAD, familial Alzheimer’s disease; Gln, glutamine; GC-MS, gas chromatography-MS; HEPE, hydroxy-eicosapentaenoic acid; HPLC-QTOF-MS, high-performance liquid chromatography quadropole-time-of-flight MS; IC-MS/MS, ion chromatography-MS/MS; LB4, leukotriene B4; LC-MS, liquid chromatography-MS; LPC, lysophosphatidylcholine; LPE, lysophosphatidylethanolamine; MS/MS, tandem mass spectrometry; mTOR, mammalian target of rapamycin; NTG, non-transgenic; PA, phosphatidic acid; PC, phosphatidylcholine; Pro, proline; PS1/PSEN1, presenilin-1; TCA, tricarboxylic acid; Thr, threonine; TMCA, tauromuricholic acid; TREM2, triggering receptor expressed on myeloid cells 2; UDP, uridine diphosphate; UHPLC, Ultra high-performance liquid chromatography; UPLC-MS/MS, ultra performance liquid chromatography-MS/MS; WT, wild type.