Table 3.
Comparison of case-control lipidomic studies reporting alteration of sphingomyelin (SM) species in neurodegenerative diseases.
| Disease | Alzheimer’s Disease (AD) | Parkinson’s Disease (PD) | Multiple Sclerosis (MS) | Amyotrophic Lateral Sclerosis (ALS) | ||
|---|---|---|---|---|---|---|
| Reference | [47] | [53] | [54] | [55] | [56] | |
| Matrix | Plasma | CSF | Plasma | CSF | Plasma | |
| Cohort | State/type of disease (n) | Mild or moderate * (26) | Mild or moderate * (16) | Early disease state (77) |
CIS, RRMS, PPMS (20) | Study 1 (62) Study 2 (99) |
| criteria for controls (n) | cognitively normal (26) | cognitively normal (10) | cognitively normal (69) | OND (17) | cognitively normal Study 1 (69) Study 2 (48) |
|
| Platform | ESI/MS/MS | MALDI/MS-MS | UHPLC/QTOF/MS | LC-ESI-MS/MS | UHPLC/MS/MS | |
| Sphingoid base identified | no | yes | no | yes | no | |
| Statistics | Wilcoxon rank sum test | Kruskal-Wallis; best separation peaks | PLS and RF selection followed by univariate tests | PLS-DA; unpaired t-test | Welch’s two-sample t-test | |
| Covariates | no | no | age, gender | no | no | |
| Multiple comparison’s correction | no † | no | yes | no | yes | |
| Sphingomyelins | ||||||
| Sphingoid base not identified: N-linked fatty acid | ||||||
| SM N17:1, 18:0, 24:2 | ns | |||||
| SM N20:0, 21:0, 22:0, 23:0, 24:0, 22:1, 23:1, 24:1 |
↓ | |||||
| Sphingoid base not identified: Hydroxyl Group Level | ||||||
| SM d30:1, 32:1, 39:1 | (↓) | |||||
| Sphingoid base identified | ||||||
| SM d18:1/13:0, 14:0, 16:0, 16:1 (9Z)(OH) | ↓ | |||||
| SM d18:1/18:0 | ↑ | |||||
| SM d18:1/24:1 (15Z) | ↓ | ↓ | ||||
| SM d18:2/20:0, 22:1 | ↓ | |||||
* Mini-Mental State examination (MMSE). † Q values (cumulative false discovery rates) were evaluated. CIS: clinically isolated syndrome; CSF: cerebrospinal fluid; ESI: electrospray ionization; LC: liquid chromatography; MALDI: matrix-assisted laser desorption/ionization; MS (in platform): mass spectrometry; PPMS: primary-progressive MS; QTOF: quadrupole time-of-flight; RRMS: relapsing-remitting MS; UHPLC: ultra high performance liquid chromatography. Statistics. PLS-DA: partial least square-discriminant analysis; RF: random forest. ↑/↓: significantly increased/decreased in disease subjects; ns: non-significantly altered; (↓): SM species significantly altered between controls and PD patients according to the PLS model, but with p-values > 0.05 in subsequent Welch’s t-test or Wilcoxon test false discovery rate (FDR) adjusted. Empty cells indicate that the lipid species was not evaluated in the corresponding study.