Alzheimer's Disease (AD), affecting 30 million people globally and representing 60% of dementia cases, remains a major societal challenge. Whilst there is ongoing debate on the contribution of different disease mechanisms, currently no effective treatment is available to stop or reverse cognitive decline, thus altering disease progression. Our research explores a new pathway of resilience to AD through the study of Rab10, a protein involved in transport inside neurons. Indeed, a rare variant of Rab10 has been shown to confer protection against dementia in high-risk individuals, although the precise mechanism is still unknown. This project builds on previous results of our group investigating how Rab10 coordinates the transport of key signalling molecules within nerve cells, which is crucial for maintaining healthy brain function. By focusing on a specific modification of Rab10 triggered by another key brain factor, LRRK2, we now aim to understand how this influences its ability to support neuronal resilience to AD. Our research will employ advanced imaging and biochemical techniques to study these processes in rodent and human nerve cells. Furthermore, we will test the effects of genetic alterations and drug treatments that could enhance this protective pathway in a cell model of AD in Down Syndrome (DS), a condition that involves a nearly 100% risk of developing AD. Focusing on mechanisms of neurological resilience, this research could open new avenues for the development of treatments targeting the underlying mechanisms of AD.