Table 1.

Protein biomarkers of ALS in biofluids

Name, accession number	Pathological association	Size (kDa)	Biofluid	Change in ALS	Detection technique	Link to disease
p75ECD, P08138	Neurodegeneration	30–50	Urine	Increase	WB, LC-MS, ELISA	Prognostic, correlated to ALSFRS-R, increases longitudinally over disease progression.38-40
NfL, P07196	Neurodegeneration	61–68, 22	CSF, serum, blood	Increase	Immunoassay, ELISA, SIMOA, WB	Prognostic, correlated to ALSFRS-R and progression rate.15,41-44 NA for whole blood WB.45
pNfH, P12036	Neurodegeneration	190–210	CSF, serum	Increase	ELISA, SIMOA	Prognostic, correlated to ALSFRS-R and progression rate.15,41,46,47
Titin, Q8WZ42	Muscle degeneration	∼23	Urine	Increase	ELISA	Prognostic, especially for lower limb ALS.48
C9ORF72: poly-glycine-proline, NA	Disease specific	ND	CSF	Increase	ELISA	Related to repeats,49-51 not disease.50
TDP-43, ratio pTDP: TDP, Q13148	Disease specific	45, 43–50	Plasma, CSF	Increase or NA	SIMOA, WB, LC- MS, ELISA	Improves diagnosis in combination with NfL in SIMOA assay.52 Relationship to disease NA.53,54 Ratio pTDP: TDP, no correlation to disease.55
FUS, P35637	Disease specific	53	Plasma	Increase	WB	Relationship to disease not investigated.54
SOD1, P00441	Disease specific	15.4	Plasma	Increase	WB	Relationship to disease not investigated.54
pTau and tTau, P10636	Other	40–60	CSF	Increase	Immunoassay	tTau and pTau/tTau prognostic.56
Collagen, P53420	Other	164	Serum, urine	Decrease	Radioimmunoassay	Correlated to disease duration.57,58
MCP-1, P13500	Immune system	11–13	CSF, serum	Increase, NS	ELISA	CSF prognostic.16,59-61
CXCL13, O43927	Immune system	13	CSF	Decrease	Immunoassay	Relationship to prognosis and ALSFRS-R not investigated.62
CHIT1, Q13231	Immune system	51	CSF	Increase	LC-MS, ELISA	Prognostic, correlated to disease progression.59,63-66
CHI3L1, P36222	Immune system	40	CSF	Increase	LC-MS, ELISA	Prognostic, correlated to progression.59,65,66
CHI3L2, Q15782	Immune system	39	CSF	Increase	LC-MS	Correlates to disease progression.66
C reactive protein, P02741	Immune system	22	CSF, serum	Increase/NS	LC-M, ELISA/mesoscale	Significant in CSF.67 NS in CSF/serum.16 Serum levels increased in ALS;68 prognostic.69
IL-6, P05231	Immune system	21–28	CSF, serum	Increase/NS	ELISA/immunoassay	CSF correlated to duration70/NS.16 Increased in serum.71
IL-18, Q14116	Immune system	23	CSF	Increase	Immunoassay	Correlated to progression and changes over progression.16
TNF-α, P01375	Immune	17	CSF, serum	Increase	Immunoassay	Not consistently associated with ALS prognosis or progression.71,72
Cystatin C, P01034	Immune system	13.3	CSF	Decrease	ELISA	Correlated to survival, prognostic.73-75
Native transthyretin, CysGly, P02766	Immune system	55 69	CSF CSF	Decrease Increase	LC-MS	Relationship to ALS not tested.76 CysGly—transthyretin does not change over ALS progression.67
sCD14, P08571	Immune system	40	CSF, serum, urine	Decrease Increase	ELISA	Lower CSF CD14 associated with poor prognosis.77 Elevated in CSF, urine and serum. Serum sCD14 prognostic.68

LC, liquid chromatography; MS, mass spectrometry; NA, not applicable; NS, not significant; WB, western blot.