Neutrophil Extracellular Traps Induced Glial Type I Interferon in the Pathogenesis of Tauopathy

Tauopathies, including Alzheimer’s Disease (AD), characterized by the brain accumulation of abnormal Tau proteins, represent a significant unmet medical need. Neuroinflammation is a hallmark of these diseases. Although several neuroimmune regulations, notably involving microglia, have been largely studied recently, the role of neutrophils and the release of neutrophil extracellular traps (NETs) has been overlooked. The TNT project will fill the gap as aimed to (1) characterize the temporal dynamics of neutrophil and NETs involvement vs. Tauopathy progression and (2) evaluate the functional impact of NETs and type I interferon (IFN-I) on disease pathogenesis. Using a combination of approaches, including Tauopathy and Tau seeding models together with post-mortem tissue of patients with primary Tauopathy, the TNT project will advance our understanding of the complex interplay between NETs, glial and Tau pathology, potentially leading to novel therapeutic strategies. The project will study the influence of the biological sex on these mechanisms and assess their therapeutic potential.The host institute provides a robust platform for bidirectional knowledge exchange, with expertise in Tau transgenic and seeding models, 3D glial cell reconstitution, and inflammasome-Tau pathology, significantly enhancing our research on glial cell changes. My expertise in neuroimmunology and neutrophil biology, will be instrumental in advancing ongoing projects at the host lab. The planned training will enhance my research skills while fostering independence, mentorship, and communication abilities, preparing me for leadership. Engaging in mentorship activities and workshops will equip me with skills to guide and inspire junior researchers, and enhance my ability to communicate complex concepts to diverse audiences. This development will position me as a young leader in neurodegenerative diseases, ready to make significant contributions to scientific advancement and knowledge transfer.