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Amyotrophic lateral sclerosis (ALS) is an idiopathic fatal neurodegenerative disease that is characterized by the loss of upper and lower motor neurons. Inflammation is widely recognized as a hallmark of this disease; however, the intricate relationship between immune biomarkers and the pathogenesis of ALS is not fully understood yet. In this multidisciplinary thesis, by integrating multiple cohorts and employing diverse research methodologies, we delved deeper into the complex interplay of immune system dynamics and its impact on the risk, progression, and outcomes of this debilitating neurodegenerative disease. Study I conducted within a longitudinal population-based cohort explored the associations between blood and urine biomarkers and the future risk of ALS and Parkinson’s disease (PD). Although increasing concentrations of leukocytes, haptoglobin, and uric acid were associated with a lower risk of PD, no statistically significant associations were noted between the studied biomarkers and the risk of future ALS diagnosis. By analyzing repeated biomarker measurements, the study described the temporal changes of these biomarkers during the two decades preceding the diagnosis of these diseases, shedding light on the dynamic nature of the immune biomarkers during disease development. While levels of leukocytes and uric acid were consistently lower in PD cases compared to controls, we did not observe any consistent differences in the studied biomarkers between ALS cases and their matched controls. Study II investigated the contribution of T cell responses to disease pathology by using flow cytometric analysis of blood and cerebrospinal fluid (CSF) samples from a cohort of newly diagnosed ALS patients. Our findings suggested that T cell phenotypes, at the time of diagnosis, have the potential to serve as predictors of disease outcomes. A high frequency of CD4+FOXP3- effector T cells in both blood and CSF was associated with poor survival, while a high frequency of ac