Table 4.

Potential inflammatory, genetic, and miRNA biomarkers for use in ALS clinical trials

Biomarker	Prognostic value
Inflammatory
CHIT1	Elevated in the CSF of patients with ALS vs controls/other neurological diseases Levels correlate with rate of progression75
FoxP3	Tregs that downmodulate inflammatory responses are inversely correlated with rate of ALS progression Transcription factor FoxP3 is required for Treg suppressive function Early reduced FoxP3 levels predict rapid future progression and shortened survival76
Genetic
LILRA2, ITGB2, and CEBPD expressed in peripheral lymphocytes	Expression levels were predictive of rate of ALS progression in microglia and lymphoblastoid cell lines77
SOD1 mutations	Correlate with disease severity; mutant SOD1 proteins in intracellular inclusions and CSF are cytotoxic78 A4V (SOD1A4V) has an exceptionally aggressive disease course, with shorter disease duration and lower median survival than other SOD1 mutations79
TDP‐43 mutations	Higher in the CSF of patients with FTD‐ALS spectrum disorder compared with controls25
miRNA
CSF miRNA	Used as biomarkers for many cancers and neurodegenerative disorders26, 27, 28
miR‐132	Binds TDP‐43 and modulates development and maturation of axons and dendrites Neuroprotective in tauopathies via a caspase 3‐mediated mechanism Downregulated in sALS or a subset of fALS cases80, 81
miR‐146a	Negatively regulates innate immunity in astrocytes, glia, and Tregs82, 83, 84 Abundantly expressed in human CSF27

Abbreviations: ALS, amyotrophic lateral sclerosis; CEBPD, CCAAT/enhancer‐binding protein δ; CHIT1, chitotriosidase; CSF, cerebrospinal fluid; fALS, familial ALS; FTD‐ALS, frontotemporal dementia‐ALS; FUS, fused in sarcoma; ITGB2, integrin subunit β 2; LILRA2, Leukocyte immunoglobulin‐like receptor subfamily A member 2; miRNA, micro‐RNA; sALS, sporadic ALS; SOD1, superoxide dismutase 1; TDP‐43, transactive response DNA binding protein 43 kDa; Treg, T regulatory cell.