Cerebrospinal fluid: Profiling and fragmentation of gangliosides by ion mobility mass spectrometry

Developments and applications of separation and microfluidics methods coupled to electrospray mass spectrometry in glycomics of nervous system gangliosides

“…In view of the reduced expression of gangliosides in CSF as compared to brain tissue [86–88], the detection of low abundant glycoforms, which solely by separation according to m/z would have remained undetected, is of major analytical and biological importance. Following the drift time retention for each class of gangliosides, the elevated degree of sialylation identified in CSF (more than 76%), specific to brain tissue as well (over 78%) [20,72,73], together with the polysialylated glycoforms in the GT1>GQ1>GD1 descending series characteristic for both CSF and brain [63], support the previous data related to the similarity of ganglioside expression in CSF and brain [74]. Further evidence in this regard was supplied by the discovery in CSF of gangliosides modified by O‐ Ac and Fuc, which also characterize the brain tissue [20,72,73]; more than a half of such gangliosides detected in different brain regions were also identified in CSF [74].…”

“…Following the drift time retention for each class of gangliosides, the elevated degree of sialylation identified in CSF (more than 76%), specific to brain tissue as well (over 78%) [20,72,73], together with the polysialylated glycoforms in the GT1>GQ1>GD1 descending series characteristic for both CSF and brain [63], support the previous data related to the similarity of ganglioside expression in CSF and brain [74]. Further evidence in this regard was supplied by the discovery in CSF of gangliosides modified by O‐ Ac and Fuc, which also characterize the brain tissue [20,72,73]; more than a half of such gangliosides detected in different brain regions were also identified in CSF [74]. In view of these results, obviously this approach might be further applied in clinical research for determination of molecular fingerprints valuable for early diagnosis of CNS disorders, monitoring of the biochemical changes associated to disease progression/regression, or tracking treatment effectiveness [74].…”

“…Consequently, IMS it is able to separate isomers, isobars, and conformers, as well as to provide information on the stoichiometry, topology, and structures with biomarker value in highly complex mixtures, as no other separation technique. In combination with an efficient fragmentation method, such as CID [37,72–74], electron transfer dissociation [75], or negative electron transfer dissociation [76], IMS MS results in a unique and highly versatile method capable of separation, detection by MS, and structural characterization of even minor compounds, in a complex mixture of biopolymers in a single run and on a single instrument. Apart from these advantages, since in the case of commercial instruments the IMS module is incorporated into the mass spectrometer, the shortcomings related to the MS coupling via an interface are also eliminated.…”

“…In view of the (i) restricted access to brain biopsies or tumor tissue specimens; (ii) previous data related to the similarity of ganglioside content in CSF and brain; and (iii) permanent physical contact of CSF with the brain and spinal cord and its daily renewal, CSF ganglioside mapping may provide valuable data related to the pathophysiological state of the CNS. If in the past CSF glycolipids could be approached primarily by quantification of the main classes, recently nano‐ESI‐IMS MS offered detailed information upon CSF gangliosidome [74]. (‐) Nano‐ESI‐IMS‐MS of gangliosides extracted from CSF of adult individuals exhibiting no signs of tumors, demyelination, intracranial hemorrhage or acute inflammatory process evidenced no less than 113 distinct species, which are analogous to the species detected by IMS MS in the normal human brain.…”

“…Further evidence in this regard was supplied by the discovery in CSF of gangliosides modified by O‐ Ac and Fuc, which also characterize the brain tissue [20,72,73]; more than a half of such gangliosides detected in different brain regions were also identified in CSF [74]. In view of these results, obviously this approach might be further applied in clinical research for determination of molecular fingerprints valuable for early diagnosis of CNS disorders, monitoring of the biochemical changes associated to disease progression/regression, or tracking treatment effectiveness [74].…”