Over 12 million people in Europe suffer from neurodegenerative diseases (ND), yet treatments that prevent or stop the progression of neurodegeneration are still lacking. Tackling this grand challenge requires enhanced coordination of national efforts to accelerate discovery. Such synergies have been created among 28 countries in the pilot EU JPI on Neurodegenerative Disease Research (JPND). JPND has a long standing experience in collaborative action with €75 million of additional national funds being successfully mobilized between 2011 and 2014 to support transnational research programs. The JPND Research Strategy is now ripe for further enhancement in tight coordination with the EC through an ERA-Net Cofund instrument JPco-fuND with an unprecedented commitment of €30 million of national funds associated to a highly incentivizing EC top-up fund. Among the most burning questions, three priority topics have emerged through a consultative process between researchers and JPND members in order to unlock several major issues within ND research: the identification of genetic, epigenetic and environmental risk and protective factors, the development and maintenance of longitudinal cohorts, the creation of advanced experimental models. These are key questions of equal priority to increase understanding of ND mechanisms that will be addressed through a common joint transnational call allowing a significant acceleration of the execution of the JPND research strategy. Moreover, to expand the impact of JPco-fuND, JPND will continue to implement other actions without EU co-funding such as aligning national research strategies, making databases more accessible and interoperable, developing enabling capacities such as supportive infrastructure and platforms, capacity building, education and training. These actions are required in parallel to achieve the highest impact for the patients, their carers and for society as whole and address this grand challenge in the coming years.