A systems immunology analysis of Alzheimer’s disease reveals an age- and environmental exposure-independent disturbance in B cell maturation

Alzheimer’s disease is a severe neurodegenerative disorder, with multifactorial mechanisms of disease development and progression. Evidence from genetic association studies, animal models, and clinical investigation suggests a neuroimmunological component to disease, with links to the peripheral immune system. Here we applied a systems immunology approach to determine the immunological correlates of Alzheimer’s disease. Using high-dimensional flow cytometry and machine learning, we comprehensively assessed the cellular component of the peripheral immune system in a well-characterised cohort of 184 Alzheimer’s patients and 105 healthy spouses. Using this approach, Alzheimer’s patients demonstrated a disturbance in B cell maturation, a feature which was associated not only with disease status but also with cognitive decline. This effect was age– and environmental exposure-independent, suggesting a disease-intrinsic relationship between Alzheimer’s disease and B cell maturation. These results provide an under-explored avenue for both improving both mechanistic understanding and therapeutic design in Alzheimer’s disease.