This study investigates the causal relationships between immune cells and neurodegenerative diseases (NDs) using a two-sample Mendelian randomization (MR) analysis. The research analyzed 731 immune cell features and four NDs: Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). The study utilized genetic variants as instrumental variables to assess the causal links between immune cell characteristics and the risk of these diseases. The results identified potential causal relationships between various immune cell types and the four NDs. Specifically, 8 immune cell types were associated with AD, 1 with PD, 6 with ALS, and 6 with MS. The study found that certain immune cell features, such as CD33 expression on specific cell types, showed positive associations with AD, while others showed negative associations. For PD, CD11c on monocytes showed a positive association. For ALS, several immune cell types showed negative associations. For MS, one immune cell type showed a positive association. The study used multiple MR methods, including inverse variance weighted (IVW), weighted median, MR-Egger, and Wald ratio tests, to ensure robustness and minimize bias. The findings suggest that immune cells play a significant role in the pathogenesis of NDs, providing new insights for future clinical research and treatment strategies. However, the study has limitations, including the potential bias due to the European ancestry of the study population and the lack of individual-level data for further stratification. The study highlights the importance of immune cell function in NDs and suggests that targeting specific immune cells could be a promising approach for treatment.This study investigates the causal relationships between immune cells and neurodegenerative diseases (NDs) using a two-sample Mendelian randomization (MR) analysis. The research analyzed 731 immune cell features and four NDs: Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). The study utilized genetic variants as instrumental variables to assess the causal links between immune cell characteristics and the risk of these diseases. The results identified potential causal relationships between various immune cell types and the four NDs. Specifically, 8 immune cell types were associated with AD, 1 with PD, 6 with ALS, and 6 with MS. The study found that certain immune cell features, such as CD33 expression on specific cell types, showed positive associations with AD, while others showed negative associations. For PD, CD11c on monocytes showed a positive association. For ALS, several immune cell types showed negative associations. For MS, one immune cell type showed a positive association. The study used multiple MR methods, including inverse variance weighted (IVW), weighted median, MR-Egger, and Wald ratio tests, to ensure robustness and minimize bias. The findings suggest that immune cells play a significant role in the pathogenesis of NDs, providing new insights for future clinical research and treatment strategies. However, the study has limitations, including the potential bias due to the European ancestry of the study population and the lack of individual-level data for further stratification. The study highlights the importance of immune cell function in NDs and suggests that targeting specific immune cells could be a promising approach for treatment.