Cerebrospinal Fluid and Blood Biomarkers of Neuroaxonal Damage in Multiple Sclerosis

Table 5

Membrane and nuclear biomarkers of neuroaxonal damage in the cerebrospinal fluid (CSF) and blood of patients with multiple sclerosis (MS) and/or clinically isolated syndrome suggestive of MS (CIS).

Biomarker; (subtype)	Body fluid	Immunoassay	Number of patients	Main findings	REF
BACE1; (membrane)	CSF	Enzymatic	100 MS (RR/SP/PP)	MS slightly↓NHCo	[122]
Apo- E; (membrane)	CSF/SE	Immunofluorometry	34 MS	CSF levels in MS ↓↓ NHCo	[159]
	CSF	2DE-MS	10 RRMS + 11 CIS	one isoform expression in RR ↑↑ CIS or NHCo	[161]
	CSF/SE	Immunoturbidimetry	33 MS (RR)	CSF/serum index in MS in remission ↑↑ NHCo	[160]
GAP-43; (membrane)	CSF/SE	xMap Bead –based	49 MS (RR/SP/PP)	CSF in RR ↔ SP ↔ PP ↔ OIND + NIND + HCo, not detected in serum	[167]
	CSF	xMap Bead –based	44 MS (RR/SP/PP)	significant positive correlation with NAA levels	[141]
24S-OH-chol; (membrane)	PL	IDMS	46 MS (RR/PP)	negative correlation with T2 lesion volume	[169]
	PL	IDMS	11 MS	MS ↔ HCo	[170]
	CSF/PL	IDMS	118 MS (RR/SP/PP)	PL levels in older MS ↓↓ HCo	[171]
	SE	IDMS	60 MS (RR/SP/PP)	PP or older RR ↓ HCo	[172]
	CSF/PL	IDMS	88 MS	PL levels in MS ↔ Co	[173]
Protein 14-3-3; (cytoplasmic, nuclear, membrane)	CSF	Western blot	22 MS (RR/SP/PP) + 15 ATM	detected in about 8% RR/ATM patients	[174]
	CSF	Immunoblot	38 CIS	detected in 13% CIS patients	[175]
	CSF/SE	Immunoblot	21 CIS	detected in 1/21 patient	[105]
	CSF	ELISA	114 MS (RR/SP/PP)	detected in 22% MS patients, not detected in HCo	[108]
	CSF	Immunoblot	43 MS (RR/SP/PP/PR) + 20 CIS	detected in 38% CIS/MS, similar in MS subgroups	[140]
	CSF	Immunoblot	85 CIS	detected in 8.2 % CIS patients	[176]

REF: reference; BACE1: β-site amyloid precursor protein-cleaving enzyme 1; Apo-E: Apolipoprotein-E; GAP-43: growth-associated protein-43; 24S-OH-chol: 24S-hydroxycholesterol; SE: serum; PL: plasma; Enzymatic: Enzymatic solution-based assay; 2DE-MS: two-dimensional electrophoresis-mass spectrometry; IDMS: isotope-dilution mass spectrometry; ELISA: Enzyme-Linked Immunosorbent Assay; RR: relapsing-remitting MS; SP: secondary-progressive MS; PP: primary-progressive MS; ATM: acute transverse myelitis; NAA: N-acetylaspartate; ↓ lower than; ↓↓ significantly lower than; ↑↑ significantly higher than; ↔ no difference between; NHCo: neurologically healthy controls; OIND: other inflammatory neurological diseases; NIND: noninflammatory neurological disorders; HCo: healthy controls; Co: controls with idiopathic headache.