Next, we identified a unique immune–metabolic plasma molecular signature associated with fast progressing ALS, characterized by: (i) elevated levels of soluble TNF receptor II (sTNF-RII) and C-C motif chemokine ligand 16 (CCL16), (ii) further decrease in plasma levels of leptin when compared to slow sALS. This evidence concerns the gene LEP and amyotrophic lateral sclerosis.