Plasma CHI3L1 in Amyotrophic Lateral Sclerosis: A Potential Differential Diagnostic Biomarker.

(1) Background: Motor neuron diseases (MNDs) are fatal neurodegenerative diseases. Biomarkers could help with defining patients' prognoses and stratifications. Besides neurofilaments, chitinases are a promising family of possible biomarkers which correlate with neuroinflammatory status. We evaluated the plasmatic levels of CHI3L1 in MNDs, MND mimics, and healthy controls (HCs). (2) Methods: We used a sandwich ELISA to quantify the CHI3L1 in plasma samples from 44 MND patients, 7 hereditary spastic paraplegia (HSP) patients, 9 MND mimics, and 19 HCs. We also collected a ALSFRSr scale, MRC scale, spirometry, mutational status, progression rate (PR), blood sampling, and neuropsychological evaluation. (3) Results: The plasma levels of the CHI3L1 were different among groups (p = 0.005). Particularly, the MND mimics showed higher CHI3L1 levels compared with the MND patients and HCs. The CHI3L1 levels did not differ among PMA, PLS, and ALS, and we did not find a correlation among the CHI3L1 levels and clinical scores, spirometry parameters, PR, and neuropsychological features. Of note, the red blood cell count and haemoglobin was correlated with the CHI3L1 levels (respectively, p < 0.001, r = 0.63; p = 0.022, and r = 0.52). (4) Conclusions: The CHI3L1 plasma levels were increased in the MND mimics cohort compared with MNDs group. The increase of CHI3L1 in neuroinflammatory processes could explain our findings. We confirmed that the CHI3L1 plasma levels did not allow for differentiation between ALS and HCs, nor were they correlated with neuropsychological impairment.