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Resilience and vulnerability in the cellular phase of Alzheimer’s disease.

This project proposes an integrative approach to assess how the different pathological mechanisms of AD are linked to each other and how genetic risk of AD underlays resilience or vulnerability. While the classical neuron-centric view on AD pathogenesis sees amyloid peptides as triggers of synaptic dysfunction and Tau pathology as the executor of neurodegeneration, it is now clear that other cell types also react to amyloid plaques and that the cascade leading to neurodegeneration is complex and poorly understood. Cause-consequence relationships have been difficult to establish in AD research because of the lack of a full model, but our recently developed human-mouse chimera potentially provides a game changer. We will focus on two crucial aspects of the disease: i.e. the link between amyloid-Tau-mediated neuronal death and glia-mediated neuroinflammation. We will investigate how these processes ultimately affect synaptic function, in particular in the entorhinal-hippocampal neurocircuitry, and how genetic risk modulates these cellular reactions. Our central aim is to increase fundamental insights into the molecular mechanisms leading to AD, but when breakthroughs are made, we will spend the time and effort to validate findings and translate them into novel drug targets and biomarkers.

Date:1 Oct 2000 →  Today
Keywords:neurodegenerative, Alzheimer's disease
Disciplines:Neurosciences not elsewhere classified