Whole-genome analysis led to the identification of relatively rare mutations in TREM2 gene that are associated with a high AD risk.187 Given the TREM2 is exclusively expressed in immune cells,188 and involved in the activation of immune cells by stimulating phagocytosis and reducing cytokine production, we can conclude that immune dysregulation, especially those in innate immune system, is a primary, causal contributor to the development of neurodegenerative diseases. The gene discussed is TREM2; the disease is Alzheimer disease.