Plasma lipid peroxidation biomarkers for early and non-invasive Alzheimer Disease detection

Validated analytical method to determine new salivary lipid peroxidation compounds as potential neurodegenerative biomarkers

“…For the method validation some analytical characteristics were evaluated for each analyte (limits of quantification (LOQ), limits of detection (LOD), linearity, precision, accuracy, matrix effect, stability). The LODs and LOQs, defined as the standard concentrations generating a signal-to-noise ratio of 3 and 10, respectively, as well as the linearity were evaluated in a previous study [30]. Then, saliva samples non-spiked and spiked at three concentration levels (i.e.…”

“…Some compounds were acquired from Cayman Chemical Company (Ann Arbor, Michigan, USA) (PGE 2 , PGF 2␣ , 1a,1b-dihomo-PGF 2␣ , 5-F 2t -IsoP, 15-E 2t -IsoP, 15-F 2t -IsoP, 15-keto-15-E 2t -IsoP, 15-keto-15-F 2t -IsoP, 15(R)-15-F 2t -IsoP, 2,3-dinor-15-epi-15-F 2t -IsoP, PGF 2␣ -D 4 ) and used as analytes, as in a previous study [27]. Other compounds nor available commercially were synthesized ((4(RS)-F 4t -NeuroP, 7(RS)-ST-8 -11-dihomo-IsoF, Ent-7(RS)-7-F 2t -dihomo-IsoP, 10-epi-10-F 4t -NeuroP, 14(RS)-14-F 4t -NeuroP, 17-epi-17-F 2t -dihomo-IsoP, 17-F 2t -dihomo-IsoP, 17(RS)-10-epi-SC-15 -11-dihomo-IsoF, D 4 -10-epi-10-F 4t -NeuroP) [28], and they were used as analytes, as in previous studies [29,30].…”

“…The MS detector consisted of an electrospray ionization source working in the negative mode (ESI-) and multiple reaction monitoring (MRM) mode. The UPLC-MS/MS system conditions were described in a previous work [30]. Briefly, the LC conditions were an Acquity UPLC BEH C18 column, H2O and CH3CN with 0.01% v/v CH3COOH as mobile phases, 55 • C and 4 • C as column and autosampler temperatures, 8 L as injection volume, and 0.45 mL min −1 as flow rate; and the detection conditions were 2.0 kV as capillary voltage, 150 • C and 395 • C as source and desolvation temperatures, 150 L h −1 and 800 L h -1 as nitrogen cone and desolvation gas flows, and 10 ms as dwell time.…”

Assessment of lipid peroxidation and artificial neural network models in early Alzheimer Disease diagnosis

“…The samples were processed as indicated in previous studies, where the corresponding sample treatment procedures were optimized [9,38]. Thereafter, the samples were injected into the chromatographic system (UPLC-MS/MS) following previously validated analytical methods whose chromatographic and detection conditions were described in previous works [9,38]. Finally, the levels of a new set of lipid peroxidation biomarkers (isoprostanes, neuroprostanes, dihomoisoprostanes, isofurans, neurofurans, dihomoisofurans) were obtained.…”

“…In this work we developed different multivariate models in order to improve the diagnostic utility of lipid peroxidation products from plasma and urine samples [9,38], since they do not have a high diagnostic capacity individually. For this, different multivariate models based on linear and non-linear regression were developed for each kind of biological sample and they were compared in terms of diagnostic performance.…”