PhD defence Maria Tzousi Papavergi

Keywords: Alzheimer’s disease, Complement system, Amyloid-related imaging abnormalities, Tau-driven neurodegeneration

"A flowing cascADe: Diving into complement dynamics in Alzheimer's disease"

Every 3 seconds, someone in the world develops dementia, with Alzheimer’s disease being its most common form. Two proteins, amyloid and tau, accumulate abnormally in the Alzheimer’s brain and play key roles in disease development. The complement system is a powerful component of our innate immune defense, playing a crucial role in fighting pathogens, but it is also increasingly recognized as a major “influencer” in both the healthy and diseased brain, including in Alzheimer’s disease. This thesis investigated whether reducing C3, a central protein of the complement system, could protect the brain against different aspects of Alzheimer’s disease. It examined the role of C3 in side effects associated with antibody treatments targeting amyloid, its involvement in disease processes driven by tau, and the contribution of different brain cell types to complement-related damage. Together, the findings suggest that targeting C3 may have therapeutic potential, while also revealing that the effects of the complement system are highly dependent on disease stage, treatment context and timing.

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