CSF prognostic markers for amyotrophic lateral sclerosis: a proteomic study

The rate of disease progression widely varies between patients with amyotrophic lateral sclerosis (ALS). Prognostic assessment using biomarkers is highly preferred for planning medical care and improving the design of clinical trials. Therefore, the current study aimed to assess prognostic biomarkers for predicting future functional decline in patients with ALS. The prospective progression rate was calculated using the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) at CSF collection and in 6 months. The ALS patients were classified into slow, intermediate, and fast progression groups. We performed comprehensive proteomic analyses of the CSF samples. In total, 26 proteins changed significantly (p < 0.05 and q < 0.10), with levels varying within a large dynamic range (fold change of > 1.5 or < 0.5). A receiver operating characteristic curve analyses showed that the following proteins showed high discrimination power between slow and fast progression groups: GPNMB, GFAP, GPC1, MGAT2, and CHI3L2. Of these, GPNMB, GPC1, and CHI3L2 were significantly correlated to prognostic progression rate. This study demonstrated that CSF levels of neuroinflammation and glycosylation-related proteins were significantly correlated with prospective progression rates in patients with ALS. These proteins could be useful prognostic biomarkers for ALS.