A multidisciplinary approach to study Sporadic Amyotrophic Lateral Sclerosis in patients with common geographical origin

Amyotrophic Lateral Sclerosis (ALS), a fatal neurodegenerative disorder, is object of intensive research as the causes are still unknown and a treatment not available yet. This project is aimed to study, with a multidisciplinary approach, a small cohort of ALS subjects with a common environmental exposure. For metal quantitation, samples of serum and whole blood were analyzed by ICP-MS. For proteomic analyses, immobilized pH gradient covered the 4-10 and 3-7 pH range. Arsenic concentration resulted significantly lower in patients than in controls. Also, Mn and Hg showed lower levels in patients. Levels of plasma APOA2 protein resulted decreased in patients with respect to controls, whereas SAMP showed a significant decrease only in the late onset group. APOA1 and TTHY also were decreased, the latter in late-onset patients. RET4 was decreased only in the early-onset group. When evaluating APOE genotype we found a 3-fold increase in the frequency of E3/E4 genotype in the patient’s group. DNA oxidative stress has been evaluated through a Comet Assay. The multidisciplinary approach applied in this study allowed to dissect different aspects of ALS, often are evaluated separately and in heterogeneous cohorts of patients.