Ageing, is the single greatest risk factor for neurodegenerative diseases, yet it is the most challenging to investigate at the cellular and molecular level. We have developed novel tissue systems that combine brain tissue with stem cell technology, allowing us to address how cell-autonomous and non-cell-autonomous factors modulate neuronal vulnerability to neurodegeneration.

Neuronal health is closely intertwined with that of the glial cells surrounding them and we hypothesize that aging-associated neuronal dysfunction and vulnerability to neurodegeneration are driven by glial changes. With our novel tissue systems we can now dissect the dynamics and molecular mechanisms of glial genetic risk factors of many neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, while preserving experimental amenability to test therapeutic approaches in a human(ized) system.

While cellular alterations can partially explain neurodegeneration, extrinsic factors are also involved in this process. To this end, we are investigating cerebrospinal fluid as a source of immunomodulatory factors that can directly regulate the cellular and network function and thus contribute to neurodegeneration.