Among the 28 chosen CSF constituents, 4 with the highest LASSO regression coefficients were unrelated compounds (1-methylhistidine, creatine N6-succinyladenosine, and nicotinate ribonucleoside). We couldn’t replicate the PSP-specific serum biochemical profile or any components as reported by Mori (2019). The compounds selected in uni and multivariate biochemical panels mostly lacked shared biochemical properties and didn’t map to canonical metabolic pathways. The 5-fold cross-validation ROC-AUC for PSP versus CN was 72.4%.Ĭonclusion: In CSF (and to a lesser extent in serum), global metabolomic profiling helps with diagnostic differentiation between PSP and CN. Sensitivity and specificity for CN were 88.6% and 88.2% for PSP, 82.5% and 78.7%. For serum, multinomial regression analysis selected 6 compounds with a diagnostic accuracy of 77.0%. The 5-fold cross-validation ROC- curve-AUC for PSP versus CN was 83.6%. Sensitivity and specificity for CN were 94.1% and 92.2% for PSP, 90.9% and 88.9%. CSF multinomial regression analysis selected a 12- compound panel (diagnostic accuracy: 87.8%). CSF univariate analysis (moderated t-test) selected 28 compounds (27 PSP-specific) serum provided 3 PSP-specific compounds. Results: Metabolomic profiling determined 441 CSF and 1,042 serum compounds. For characterizing selected biochemical panels discriminating PSP from CN, the multivariate analysis used several biostatistical methods. ![]() Analytes underwent univariate analysis with false discovery rate-adjusted p-value (≤0.05) determinations. Authentic standards facilitated all chemical identifications. Methods: Ultrahigh-performance liquid chromatography linked to tandem-mass spectrometry measured relative concentrations of biochemicals <1.5 kDalton molecular weight. Objective: Global metabolomic profiling of biochemicals for diagnostic differentiation of CSF and serum from 34 healthy controls (CN) and 44 patients with progressive supranuclear palsy (PSP).īackground: Though PSP lacks evidence for specific metabolic disturbances, Mori et al (PLoS ONE 2019 14(9):e0223113) reported alteration of small-molecular weight compounds in serum specimens, yielding a diagnostic biochemical profile.
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