Microglia Contribution to the Propagation of Abeta Pathology Melanie Meyer-Luehmann Department of Neurology, University of Freiburg, Germany
The progression of neurodegenerative diseases is thought to be driven by the template-directed misfolding, seeded aggregation and cell to cell transmission of disease-related proteins, leading to the dissemination of protein aggregates. More specifically, the pathogenic spread hypothesis postulates that aggregates generated in one brain region move from neuron to neuron and can thus spread into other connected areas. In support of this hypothesis, we observed that Aβ from APP transgenic host tissue is able to infiltrate and deposit within wildtype non-transgenic grafts, suggesting that neuronally produced Aβ is transported over considerable distances before it aggregates, deposits and finally leads to neurodegeneration. However, upon closer investigation of the dissemination process we were able to exclude a neuronal participation. Recent reports suggest that glial cells e.g. microglia could also be involved in protein spreading, and we therefore used neuronal transplantation techniques that allowed us to study the role of microglia in the propagation of Aβ plaque pathology. By combining novel genetic tools which manipulate microglia function with imaging approaches, we were able to address the impact of microglia in Aβ plaque formation within wild-type grafts.