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
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(128, 129) |
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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
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(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
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(132) |
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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
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(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) |
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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) |
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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) |
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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
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(137) |