As the number of patients with dementia in Japan exceeds several million, the prevention and control of this disease is an urgent issue not only medically, but also socially and economically. Genetic cohort studies in Japan and abroad have revealed genetic diversity in the onset and progression of the disease, such as polymorphisms of the APOE gene in sporadic Alzheimer's disease. The aim of this research and development is to elucidate the molecular mechanisms of variants that act protectively against dementia and to develop therapeutic seeds based on these mechanisms.