Table 3.
Components of the 24 metabolite biosignature for determining risk of phenoconversion from normal cognition to aMCI or AD.
| Metabolite name | Discovery cohort |
Internal validation cohort |
|||
|---|---|---|---|---|---|
| p-value | Log ratio (mean) | Log ratio (median) | Log ratio (mean) | Log ratio (median) | |
| PC ae C40:6 | 0.0380 | −0.3039 | −0.0809 | −0.2980 | −0.2445 |
| PC aa C40:1 | 0.0414 | −0.2040 | −0.0779 | −1.1414 | −0.1909 |
| PC aa C38:6 | 0.0365 | −0.3372 | −0.2081 | −0.9792 | −0.1445 |
| PC aa C38:0 | 0.0391 | −0.2510 | −0.0533 | −0.5129 | −0.1469 |
| PC aa C36:6 | 0.0446 | −0.3695 | −0.1270 | −0.2383 | −0.1472 |
| lysoPC a C18:2 | 0.0299 | −0.3326 | −0.0409 | −0.3801 | −0.1235 |
| C3 | 0.0031 | −0.4574 | −0.2728 | −1.2751 | −0.3337 |
| PC ae C36:4 | 0.0428 | −0.3994 | −0.0769 | −0.6625 | −0.2740 |
| C10:2 | 0.0403 | −0.4042 | −0.1914 | −0.1913 | −0.2948 |
| C9 | 0.0070 | −0.4044 | −0.2231 | −0.8499 | −0.2433 |
| PC ae C42:1 | 0.0073 | −0.4980 | −0.3428 | −1.3565 | −0.3138 |
| PC aa C38:3 | 0.0432 | −0.4141 | −0.1500 | −0.8084 | −0.2387 |
| C5 | 0.0013 | −0.2769 | −0.1959 | −0.6762 | −0.2451 |
| ADMA | 0.0163 | −0.2962 | −0.1144 | −1.0761 | −1.5794 |
| Asn | 0.0441 | −0.1788 | −0.0891 | −0.8982 | −0.1933 |
| PC aa C34:4 | 0.0346 | −0.4353 | −0.1906 | −0.1430 | −0.0835 |
| C18:1-OH | 0.0182 | −0.2676 | −0.3349 | −1.2507 | −0.2383 |
| PC ae C34:0 | 0.0148 | −0.4064 | −0.2323 | −1.2721 | −0.4404 |
| C5-OH (C3-DC-M) | 0.0003 | −0.4214 | −0.3204 | −2.1235 | −2.0212 |
| PC aa C40:5 | 0.0298 | −0.4349 | −0.1534 | −0.5866 | −0.4183 |
| PC aa C32:0 | 0.0150 | −0.4014 | −0.1843 | −1.4605 | −0.6273 |
| C16:2 | 0.0108 | 0.2767 | 0.0789 | 0.5001 | 0.0419 |
| C12:1 | 0.0001 | 0.5075 | 0.3435 | 0.8748 | 0.2055 |
| C10:1 | 0.0026 | 0.3642 | 0.2172 | 0.6121 | 0.0184 |
In the metabolites listed, C_ species (e.g., C3) denote acylcarnitines (ACs). Phosphocholine (PC) metabolites display combined numbers of carbon atoms for their two acyl groups (sn1 and sn2 positions) (e.g., C38), whereas the combined number of double bonds (unsaturation) is displayed after the colon (e.g., C38:6). Acyl group linkages to choline backbone for PCs feature ester (a) or ether (e) linkage (e.g., PC ae C36:4). Asn, asparagine. ADMA, asymmetric dimethylarginine. LysoPC, lysophosphatidylcholine species, with only one acyl group, typically in the sn1 position. The discovery cohort provided significant differentially expressed metabolites between Converterpre and NC. The column of p values indicates the significant differences for mean analyte values between the clinical groups for the discovery cohort. Log ratios represent the difference of the log-transformed values (mean or median) for Converterpre and NC subjects. Negative log values indicate that levels (mean or median) of the analyte in Converterpre < NC, while positive log values indicate that levels (mean or median) in Converterpre > NC. NC, normal control subjects.