The Complement Programme

An ambitious programme building on findings and our strengths in gene discovery, brain imaging and drug development to understand the roles of complement at different stages of Alzheimer’s Disease progression.

Gene discovery led from Cardiff has firmly implicated innate immunity, inflammation and the complement system as drivers of pathology in Alzheimer’s Disease. Beyond genetic association, involvement of complement in Alzheimer’s Disease is further supported by a large and growing body of evidence from animal studies, human biomarker and immunopathology findings and molecular pathway analyses. Complement also overlaps with and strongly influences other gene-implicated pathways such as phagocytosis, membrane turnover and debris removal, placing it at a nexus in the disease process and flagging as a potential target for therapeutic intervention.

Understanding precisely how complement contributes to the disease process in Alzheimer’s Disease, a prerequisite for effective targeting, has been more challenging. A simplistic interpretation might be that complement activation drives pathology by amplifying inflammation, activating glia and exacerbating neuronal damage. However, there is compelling evidence that complement activation can, in some circumstances, reduce or reverse Alzheimer’s Disease pathology

This is an ambitious programme building on these findings and local strengths in gene discovery, brain imaging and drug development at Cardiff University to achieve understanding of the roles of complement at different stages of disease progression in Alzheimer’s Disease models and patients. This detailed understanding will support the discovery of predictive biomarkers and guide development of safe and effective anti-complement drugs for prevention and therapy of Alzheimer’s Disease.