Cerebrospinal Fluid and Blood Biomarkers of Neuroaxonal Damage in Multiple Sclerosis

Table 4

Cytoplasmic, non-neurofilament 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	Body fluid	Immunoassay	Number of patients	Main findings	REF
Tubulin	CSF	Dot-blot	35 MS (RR/SP/PP)	MS ↑↑ OIND or NIND, PP/SP ↑↑ RR	[63]
Actin	CSF	Dot-blot	35 MS (RR/SP/PP)	MS ↑↑ OIND or NIND, PP/SP ↑↑ RR	[63]
Gelsolin	CSF/PL	Western blot	56 MS	PL levels in MS ↓↓ Co*, CSF levels in MS ↔ Co*	[96]
Tau	CSF	ELISA (t-t)	38 MS (RR) + 52 CIS	CIS ↑↑ NHCo	[25]
	CSF	ELISA (t-t)	45 MS (RR/SP/PP)	MS ↑↑ OIND + NIND, SP ↔ RR ↔ PP	[110]
	CSF	ELISA (t-t, p-t)	42 RRMS + 18 CIS	t-tau and p-tau in MS+CIS↑↑ NHCo, t-tau in CIS ↑↑ NHCo	[109]
	CSF	ELISA (t-t)	38 MS (RR/SP/PP) + 12 CIS	MS+CIS↔ NHCo	[104]
	CSF	ELISA (t-t)	76 MS (RR/SP/PP) + 38 CIS	MS/CIS ↔ NHCo	[54]
	CSF	ELISA (t-t)	114 MS (RR/SP/PP)	MS ↑↑ NIND	[108]
	CSF	ELISA (t-t)	52 MS (RR/SP/PP) + 50 CIS	MS+CIS ↑↑ NHCo, the highest in CIS	[103]
	CSF	ELISA (t-t)	20 MS (RR/progressive MS)	MS ↔ NHCo	[111]
	CSF	ELISA (t-t)	36 MS (RR/SP/PP)	MS ↑↑ NHCo	[107]
	CSF	ELISA (t-t, p-t)	25 RRMS	MS ↔ OIND or NIND	[112]
	CSF/SE	ELISA (t-t, p-t)	21 CIS	CIS ↔ Co**	[105]
	CSF	ELISA (t-t, p-t)	14 MS + 9 CIS	MS ↔ CIS ↔ NHCo	[106]
	CSF	ELISA (t-t)	43 MS (RR/SP/PP/PR) + 20 CIS	MS ↔ CIS ↔ NHCo+OND	[140]
Amyloid β42	CSF/SE	ELISA	21 CIS	CIS ↔ Co**	[105]
Amyloid β42	CSF	ELISA	14 MS + 9 CIS	MS ↑↑NHCo	[106]
Amyloid β42	CSF	xMAP	100 MS (RR/SP/PP)	MS ↓↓ NHCo	[122]
α-sAPP	CSF	Multiplex Assay	100 MS (RR/SP/PP)	MS ↓↓ NHCo	[122]
β-sAPP	CSF	Multiplex Assay	100 MS (RR/SP/PP)	MS ↓↓ NHCo	[122]
Bri2-23	CSF	SELDI-TOF	40 MS (SP/PP)	MS ↓ OND	[125]
NAA	CSF	GC-MS	76 MS (RR/SP/PP) + 38 CIS	SP ↓↓ RR/CIS, CIS ↔ RR ↔ NHCo	[54]
	CSF	GC-MS	46 MS (RR/SP/PP)	MS ↔ OND, SP ↓↓ RR	[141]
NSE	CSF	Luminescence	66 MS (RR/SP)	MS ↔ HCo	[64]
	SE	RIA	21 MS	levels within normal range	[142]
	PL	Luminescence	64 MS (RR/SP/PP)	progressive MS ↓ RR	[143]
	CSF/SE	ELISA	21 CIS	CIS ↓ Co**	[105]
	CSF	Immunoluminometry	33MS (RR/SP)	RR ↔ SP	[144]

REF: reference; APP: amyloid-precursor protein; NAA: N-acetylaspartate; NSE: neuron-specific enolase; SE: serum; PL: plasma; ELISA: Enzyme-Linked Immunosorbent Assay; t-t: total tau protein, p-t: abnormally phosphorylated tau protein; xMAP: xMap Bead-based immunoassay; SELDI-TOF: Surface-Enhanced Laser Desorption/Ionization Time-Of-Flight; GC-MS: stable isotope dilution gas chromatography-mass spectrometry; RIA: radioimmunoassay; RR: relapsing-remitting MS; SP: secondary-progressive MS; PP: primary-progressive MS; ↑↑ significantly higher than; ↓↓ significantly lower than; ↓ lower than; ↔ no difference between; OIND: other inflammatory neurological diseases; NIND: noninflammatory neurological disorders; Co: controls with *idiopathic headache, Bell’s palsy and ischialgia or **idiopathic headache and migraine; NHCo: neurologically healthy controls; OND: other neurological diseases; HCo: healthy controls.