Abstract

Abstract Amyotrophic lateral sclerosis (ALS) is a debilitating and lethal neurodegenerative disorder marked by the gradual deterioration of motor neurons. Diagnosing ALS is challenging due to the lack of reliable diagnostic tools, with clinical assessment being the primary criterion. Recently, increased levels of neurofilament light chain (NF-L) in CSF have been considered a useful biomarker in disease, correlating with disease progression but not specific for diagnosis. This study utilized ELISA to measure CSF CXCL12 levels in healthy controls (HC), ALS patients, and patients with ALS-mimic disorders, assessing its potential as a diagnostic biomarker and comparing it with NF-L levels. Our results confirmed previous findings, showing increased CXCL12 levels in ALS patients compared to HC (797.07 ± 31.84 pg/mL vs. 316.15 ± 16.6 pg/mL; p=0.000) and increased CSF NF-L levels in ALS (4,565.63 ± 263.77 pg/mL) compared to HC (847.86 ± 214.37 pg/mL; p=0.000). Increased CXCL12 levels were specific to ALS, not seen in ALS-mimic conditions like myelopathies (252.20 ± 23.16 pg/mL; p=0.000), inflammatory polyneuropathies (IP) (270.24 ± 32.23 pg/mL; p=0.000), and other mimic diseases (OMD) (228.91 ± 29.20 pg/mL; p=0.000). In contrast, CSF NF-L levels in ALS overlapped with those in myelopathies (2,900.11 ± 872.20 pg/mL; p=0.821) and OMD (3,169.75 ± 1,096.65 pg/mL; p=0.63), but not with IP (1,156.4 ± 356.6 pg/mL; p=0.000). ROC curve analysis indicated significant differences between the AUC values of CXCL12 and NF-L in their diagnostic capacities. CXCL12 could differentiate between ALS and myelopathies (AUC: 0.99 ± 0.005), IP (AUC: 0.962 ± 0.027), and OMD (AUC: 1.00 ± 0.00), whereas NF-L was only effective in IP cases (AUC: 0.92 ± 0.048), not in myelopathies (AUC: 0.71 ± 0.09) or OMD (AUC: 0.69 ± 0.14). We also evaluated CXCL12 levels in plasma (ALS (2,022 ± 81.8 pg/mL) vs HC (1,739.43 ± 77.3 pg/mL; p=0.015)) but found CSF determination (AUC: 0.97 ± 0.012) to be more accurate than plasma determination (AUC: 0.65 ± 0.063). In plasma, SIMOA NF-L determination (ALS (86.00 ± 12.23 pg/mL) vs HC (12.69 ± 1.15 pg/mL); p=0.000) was more accurate than plasma CXCL12 (AUC: 0.98 ± 0.01405). These findings suggest that CSF CXCL12 levels can enhance diagnostic specificity in distinguishing ALS from ALS-mimic disorders, compared to NF-L. Larger studies are needed to validate these results, but CXCL12 determination shows promising diagnostic potential.