Table 2. Metabolic features associated with outcomes investigated using a metabolome-wide association study framework.
m/z: mass-to-charge ratio, Time: Retention time, ID score: confidence in annotation based on Schymanski scale (1 being the highest and 5 the lowest), ESI: electrospray ionization, Delta ppm: mass difference in parts per million, ρCSF: correlation coefficient for metabolite measured in CSF (this was performed in a subset of participants, n = 113), Std: identify confirmed using chemical standard. See supplemental table for complete list of features associated at FDR of 5%.
| Outcome | m/z | Time (s) | Annotation | ID score | ESI | Delta ppm | Adduct | β | FDR q-value | ρ CSF | Pathway |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Clinical AD | 203.0827 | 35.5 | Tryptophan | 1 | - | 0.49 | Std | −0.334 | 0.045 | 0.24 | Tryptophan metabolism |
| 133.0143 | 27.3 | Malic Acid | 1 | - | 0.38 | Std | 0.341 | 0.045 | TCA cycle, gluconeogenesis | ||
| 342.2649 | 109.1 | Dodecanoylcarnitine | 3 | - | 0.23 | M-H | −0.386 | 0.009 | Fatty acid oxidation | ||
| Biomarker/ pTau181 positive | 114.0663 | 33.5 | Creatinine | 1 | + | 0.96 | Std | 0.390 | 0.021 | 0.32 | Urea cycle/amino group metabolism |
| 524.3703 | 32.2 | LysoPC (18:0) | 1 | + | 1.47 | Std | −0.326 | 0.021 | Glycerophospholipid metabolism | ||
| 176.1033 | 82.9 | Citrulline | 1 | + | 1.87 | Std | 0.337 | 0.025 | 0.34 | Arginine and proline metabolism | |
| pTau181 | 203.1038 | 27.1 | Valyl-Serine | 1 | - | 0.34 | Std | −0.245 | 2.9E-04 | Glycine, serine, and threonine metabolism | |
| 114.0663 | 33.5 | Creatinine | 1 | + | 0.96 | Std | 0.251 | 6.2E-04 | 0.32 | Urea cycle/amino group metabolism | |
| 176.1033 | 82.9 | Citrulline | 1 | + | 1.87 | Std | 0.199 | 0.003 | 0.34 | Arginine and proline metabolism | |
| Aβ42/Aβ40 | 213.1497 | 242.2 | 3-Oxododecanoic acid | 3 | - | 0.38 | M-H | −0.011 | 4.0E-23 | Fatty acid metabolism | |
| 88.9881 | 236.8 | Oxalic acid | 3 | - | 0.79 | M-H | −0.006 | 5.4E-06 | Glyoxylate and dicarboxylate metabolism | ||
| 540.4982 | 22.9 | Hexacosanoyl carnitine | 3 | + | 0.81 | M + H | −0.006 | 8.1E-06 | Fatty acid oxidation | ||
| NfL | 195.051 | 33.4 | Gluconate | 1 | - | 0.15 | Std | 5.822 | 4.6E-11 | 0.52 | Pentose phosphate pathway |
| 160.0615 | 36.7 | 2-Aminoadipic acid/ N-methylglutamic acid | 1 | - | 0.12 | Std | 5.305 | 1.5E-09 | 0.16 | Lysine/Glutamate metabolism | |
| 149.0455 | 30.1 | Arabinose/lyxose/ribose/ xylose | 1 | - | 0.34 | Std | 5.030 | 2.9E-08 | 0.33 | Pentose phosphate pathway | |
| GFAP | 718.2797 | 178.4 | 5-Methyltetrahydropteroyltri glutamate | 3 | + | 0.85 | M + H | −17.369 | 0.032 | Methionine metabolism (gut bacteria) | |
| 522.3552 | 32.9 | LysoPC (18:1) | 3 | + | 0.42 | M + H | 16.776 | 0.044 | Glycerophospholipid metabolism | ||
| 405.3727 | 24.3 | Dihydroxycholestane | 3 | + | 0.02 | M + H | −16.646 | 0.044 | Bile acid biosynthesis |