It is not obvious how to define a neurodegenerative disorder. There are several challenging questions: How should the diagnosis be made? How can we be sure that symptoms do not simply reflect normal aging of the nervous system? What are the mechanisms and what are the causes? What are the perspectives of treatment for the patients? Today, given the repetitive failures of curative and preventive treatments, the purpose of the following remarks is not to provide an additional lesson on “how to find a new treatment”. Instead, the aim is to ask the difficult questions that might lead to envisaging research from another angle.