VAPB aggregates in PBMCs and peripheral mediators of inflammation: new diagnostic perspectives for ALS

Poor knowledge about ALS pathophysiology is the major reason of specific diagnostic tests absence. Many different molecular mechanisms that concur to MNs degeneration have been described and among these, inflammatory process seems to play a role in disease progression. This work was aimed to reach two objectives: to find biomarkers that can help and guide the clinical diagnostic process at an early stage of ALS and to study immune system activity in ALS patients. First we evaluated the role of VAPB, a protein involved in both sporadic (sALS) and familial (fALS) forms of ALS, as a biomarker analysing peripheral blood mononuclear cells (PBMCs) isolated from sALS patients. In the second phase of the study, neuro-inflammatory mediator’s role in disease progression was evaluated by chemokines and cytokines quantification in sera of sALS patients. The data obtained revealed interesting results useful for ALS diagnosis. In fact, a characteristic pattern of VAPB was found in all sALS patients analysed. Of note, this VAPB pattern was absent in our series of controls. The quantification of serum chemokines evidenced a peculiar behaviour of two chemokines: CXCL8 and CCL2 that we found increased in sALS compared to PD and in PD compared to sALS respectively. The analysis of inflammatory mediators in sera together with the identification of VAPB aggregates in PBMCs represent a diagnostic non-invasive, simple, fast, cheap tool useful in clinical practice and for studying ALS patho-mechanisms.