Human neuro-glia cell-based model for inter-neuronal spread of tau pathology in Alzheimer’s disease

The aim of the project is to decipher the role of glial cells of the CNS (microglia and astrocytes) on the inter-neuronal spreading of tau pathology in Alzheimer’s disease (AD).The human organoid system will be based on the co-cultivation of human neuronal and glial cells (astrocytes and microglia). This model will mimic, with limitations, the native situation in the human brain under normal and diseased conditions. It will allow analyzing how various activity profiles of glial cells (activated by LPS, poly-IC, or other immune modulators) and their communication molecules influence neurons and how it affects tau seeds spreading between neurons.

The glial cell phenotypic changes/profiles after exposure to AD tau seeds and during tau cell-to-cell transfer will be evaluated using extracellular and intracellular gene and protein markers measured on the cell surface, in cell lysates, and in the cultivation medium by transcriptomic methods (RT PCR), proteomic and immunological methods (immunocytochemical staining, ELISA, WB, flow cytometry). Tau degradation will be evaluated by tau ELISA, WB, and mass spectrometry.

Detection of signaling communication molecules between neuronal and glial will be realized directly from the cultivation medium by immunological methods (ELISA).