Table 1.
Updated list of studies analyzing ether lipid content in Alzheimer’s disease (AD).
| Tissue | Analytical Approach | Cases | Effect of AD on Ether Lipid Content | Reference |
|---|---|---|---|---|
| Human Brain Tissue | ||||
| Temporal cortex, cerebellum, caudate nuclei, substantia nigra | TLC | Ctl (9) vs. AD (9). | Decreased plasmalogens in TC, not in cerebellum, caudate nuclei and substantia nigra. | [54] |
| Frontal cortex, hippocampus, white matter | HPLC and GC | Ctl (13) vs. AD (15). | Decreased PE-plasmalogens (PE(P-)). | [55] |
| Frontal cortex, parietal cortex, temporal cortex and cerebellum (grey matter and white matter) | ESI/MS | Subjects with a spectrum of AD clinical dementia rating (CDR from 0 to 3) (n = 6 per group). | Decreased PE(P-) with increase in CDR, except in cerebellum. | [56] |
| Superior/middle frontal, Inferior parietal occipital, superior temporal, cerebellum | NMR | Ctl (6–16) vs. AD (37–43) Most of the control subjects presented concomitant neuropathological disorders. |
Increased PE(P-) in frontal and temporal cortex. | [57] |
| Frontal cortex | TLC | Ctl (26) vs. AD (39). | Decreased PE(P-). | [58] |
| Frontal cortex, temporal cortex, cerebellum | LC-MS | Ctl (14) vs. AD (30). | Decreased PC(P-). | [59] |
| Prefrontal cortex | TLC | Ctl (9) vs. AD (10). | Decreased PE(P-). | [60] |
| Gyrus frontalis | GC/MS | Human AD grouped by Braak staging of neuropathology. | Decreased PE(P-). | [61] |
| Prefrontal cortex, entorhinal cortex, cerebellum | HPLC-QQQ/Ion Trap-MS | Ctl (10) vs. AD (10) per region. AD was defined as “high probability of AD” based on NIA_RI (National Institutes of Health-Reagan Institute) criteria. |
No significant differences in any brain region for plasmalogen content. | [18] |
| Grey matter, white matter | HR-ESI-MS | Young dementia, old dementia and MCI cohort. | Decreased PE(P-) in grey matter from young dementia and old dementia. | [62] |
| Prefrontal cortex | UPLC-MS/MS | Ctl (20) vs AD (21). | Decreased PC plasmalogens (PC(P-)) species containing 18:0 and 22:6. | [63] |
| Brain-derived extracellular vesicles (BDEV) from frontal cortex | nESI-UHRAMS and HCD-MS/MS | Ctl (8) vs AD (8). | Increased specific species of PE(P-). | [64] |
| Frontal cortex (white matter and grey matter) | UPLC-ESI-QTOF-MS/MS | Middle-aged cases (Ctl group, 6) vs. sAD cases (lacking co-morbidities and concomitant brain pathologies) categorized according to Braak and Braak neurofibrillary tangle (NFT) and β-amyloid stages as ADI–II/0-A (n = 7); ADIII– IV/0-C (n = 5), and ADV–VI/B-C (n = 6) | Decreased specific PC(O-), PC(P-) and PE(P-) species in grey matter and white matter with AD progression. | [65] |
| Frontal cortex | HR-ESI-MS | Ctl (20) vs. MCI (19), EOAD (17), and LOAD (17). | Decreased serine ether GPs (PS(O-), PS(P-)). | [66] |
| Human Plasma/Serum Tissue | ||||
| Serum | LC-MS/MS | >350 non-demented subjects vs. >400 demented subjects (dementia of the Alzheimer’s type). | Decreased PE(P-) 16:0/22:6 with severity pf dementia. | [67] |
| Serum | LC-MS | Ctl (66) vs. AD patients with an ADS-Cog score between 20 and 46 (40). | Decreased PE(P-) and there is a correlation between plasmalogen depletion and cognitive decline. | [68] |
| Serum | UPLC-MS | Ctl (46), MCI (143), AD (47). | Decreased ether GPs (PC(O-)). | [69] |
| Plasma | UPLC-ESI-QTOF-MS and LC-MS/MS | Five hundred and twenty-five community-dwelling participants aged 70 and older and otherwise healthy into this 5 years observational study. Three groups were defined: normal control, aMCI/AD, and converted. | Decreased PC(O-40:6) predict phenoconvertion to either MCI or AD within a 2–3-year timeframe. | [70] |
| Plasma | MRM-SID-MS | Ctl (73) vs. phenoconverters (28). | Decreased specific PC(P-) species allow to determine the risk of phenoconversion from normal cognition to aMCI or AD. | [71] |
| Serum | LC using radioactive iodine | NE (cognitively normal elderly) (107) vs. MCOs (memory clinic outpatients) (55). | Decreased PE(P-) | [72] |
| Plasma | LC-MS | Ctl vs AD. | Decreased PE(P-), bearing the DHA moiety. | [73] |
| Serum | UPLC-QQQ-MS/MS | Ctl (199), MCI (356), AD (175). | Increased specific ether-linked PCs in earliest AD. | [74] |
| Plasma | UFLC-MS/MS | From 606 participants, two groups are generated: aged controls and probable AD after 30, 60 and 90 months (ctl vs. aging and phenoconversion to AD). | Increased lysoPAF and PC(P-). | [75] |
| Plasma | HILIC-ESI-IT-TOF-MS | Ctl (41) vs. Cognitive Impairment (41). | Decreased PE(P-), especially with PUFAs. | [76] |
| Plasma | HPLC-QQQ-MS | Two cohorts: 1) Ctl (768), MCI (131), AD (211); 2) Ctl (200), MCI (400), mild AD (200). | Decreased PE(O-) and PE(P-) species. | [77] |
| Plasma | LC ESI-QQQ MS/MS | Preclinical and prodromal AD cases from the ADNI cohort (529 participants). | Decreased content of ether-linked GPs. | [78] |
Abbreviations: AD, Alzheimer’s disease; ADAS-cog, Alzheimer Disease Assessment-Cognitive; ADNI, Alzheimer’s Disease Neuroimaging Initiative database; GP, glycerophospholipids; Ctl, healthy control group; CDR, clinical dementia rating; MCI, mild cognitive impairment; EOAD, early-onset Alzheimer’s disease; LOAD, late-onset Alzheimer’s disease; UPLC-ESI-QTOF-MS/MS, ultra-performance liquid chromatography electrospray ionization quadrupole time of flight-tandem mass spectrometry; LC ESI-QQQ MS/MS, liquid chromatography electrospray ionization triple-quadrupole tandem mass spectrometry; HR-ESI-MS, high-resolution electrospray mass spectrometry; GC, gas chromatography; HPLC, high-performance liquid chromatography; TLC, thin-layer chromatography; UPLC, ultra-performance liquid chromatography; MS/MS, tandem mass spectrometry; nESI-UHRAMS and HCD-MS/MS, direct-infusion nano-electrospray ionization (nESI)—ultrahigh resolution and accurate mass spectrometry (UHRAMS) and higher energy collision induced dissociation tandem mass spectrometry (HCD-MS/MS) shotgun lipidome analysis; HPLC-QQQ-MS, high-performance liquid chromatography- triple-quadrupole mass spectrometry; LC-MS/MS, liquid chromatography tandem mass spectrometry; GC/MS, gas chromatography mass spectrometry; NMR, nuclear magnetic resonance; UFLC-MS/MS, ultra-fast liquid chromatography tandem mass spectrometry; HILIC-ESI-IT-TOF-MS, LC-MS method based on the hydrophilic interaction liquid chromatography electrospray ionization-ion trap-time of flight-mass spectrometry; MRM-SID-MS, multiple reaction-monitoring stable isotope-dilution mass spectrometry.