Table 1.
Biomarkers of Axonal Damage.
| Potential Biomarker | Study Population (n) | Sample | Results | Possible Utility |
|---|---|---|---|---|
| NfL | RRMS (65), SPMS (10), PPMS (20) | CSF | Correlated with RRMS progression to SPMS [42] | Predictive, prognostic, treatment response |
| RRMS (41), SPMS (25), controls (50) | CSF | Increased during active and acute relapse in MS patients compared to healthy controls [43] | ||
| RRMS (62), SPMS (3) PPMS (16), CIS (48), RIS (13), controls (87) | CSF, serum | Strong associated between CSF and serum levels; serum levels lower with disease-modifying treatment; serum levels positively correlated with age and higher in older patients during relapse and associated with higher risk of relapse and EDSS worsening [45] | ||
| RRMS (435), SPMS (54), PPMS (25), CIS (93) | Serum | Lower levels associated with active treatment, with larger decreases in NfL levels with high-potency treatments. Associated with T2 lesion volume over time; no association between higher levels at disease onset and higher long-term EDSS scores nor any association with relapse activity overtime; large overlap between the baseline level in MS patients and controls who may have migraine or conversion disorder [47] | ||
| RRMS (15) | Serum | Associated with clinical or MRI disease activity [48] | ||
| SET cohort: RRMS (163) GeneMSA cohort: RRMS (179) |
Serum | Lower levels associated with lower probability of recent imaging disease activity; higher levels associated with higher number of active MRI lesions [49] | ||
| RRMS (35), PPMS (17), CIS (15) | Serum | Higher baseline levels associated with higher hazard ratio of developing EDSS ≥ 4 after 15+ years [51] | ||
| MS (60) | Serum | Levels were increased six years prior to onset of MS [52] | ||
| MS (955) | Serum | Levels were elevated only after EBV seroconversion [53] | ||
| Tau | MS (25), controls (67) | CSF | Correlated with prominence of clinical symptoms [59] | Predictive, prognostic |
| Probable or confirmed RRMS (32) | CSF | Correlated with quicker disease progression and predicts time of next relapse [60] | ||
| CIS (21), controls (20) | CSF, serum | No difference between CIS patients and controls; no correlation with EDSS scores [62] | ||
| RRMS (38), CIS (52), controls (25) | CSF | Correlated with EDSS in both CIS and RRMS patients; higher correlated with conversion of CIS into clinically defined MS; associated with the number of T2-lesions on MRI [63] | ||
| RRMS (32), SPMS (2), PPMS (4), CIS (12), controls (19) | CSF | Similar levels among all clinical sub-groups and controls [64] | ||
| CIS (20), CDMS (43), controls (56) | CSF | Similar concentrations between those with demyelinating disease and controls [68] | ||
| APP | MS (6), controls (6) | CSF | Higher in MS patients compared to controls; MS patients with axons that are positive for APP are correlated with CNS lesion development [66] | Associated marker |
| TUBβ | RRMS (24), SPMS (7), PRMS (1), PPMS (1) | CSF | Higher in MS patients than patients with other neurological diseases [67] | Associated marker |
n = sample size; NfL = neurofilament light chain; APP = amyloid precursor protein; TUBβ = tubulin beta; MS = multiple sclerosis; RRMS = relapsing-remitting multiple sclerosis; SPMS = secondary progressive multiple sclerosis; PPMS = primary progressive multiple sclerosis; CIS = clinically isolated syndrome; RIS = radiologically isolated syndrome; CDMS = clinically defined MS; PRMS = progressive relapsing MS; CSF = cerebrospinal fluid; EDSS = Expanded Disability Status Scale; MRI = magnetic resonance imaging; EBV = Epstein-Barr Virus; CNS = central nervous system.