Pathways common to brain development and ageing: defining strategies for preventive therapy and diagnostics

The increasing number of elderly people will have a major impact on the prevalence of age-related diseases, which will pose major challenges to keep health systems in Europe sustainable. Current knowledge is insufficient to identify the transition of normal brain ageing into Alzheimer`s Disease (AD)-like brain damage. Elucidation of the genes and pathways contributing to the earliest stages of AD pathology and associated neurodegeneration should be instrumental to allow intervention when the condition is still reversible. The aim of the DEVELAGE project is to characterise shared molecular pathways between early developmental processes in the brain and brain ageing. Our concept is based on the hypothesis that disorders of neural development contribute to age-related neurodegeneration, that developmentally essential proteins might have a role in neurodegeneration, and that neurodegeneration-related proteins and genes are important during the development of the brain. The DEVELAGE approach is unique in that it is brain tissue-based, derived from neuropathological diagnosis with detailed molecular analysis of the spectrum of developmental and ageing changes in the very same brain samples used for a comprehensive array of investigations in humans as well as in experimental models at genetic, epigenetic, transcription and protein levels. DEVELAGE contributes to the understanding of biological variation by examining relevant number of cases with different phases of ageing and neurodegeneration as well as developing brains with or without developmental disorders. Pathways examined in humans will be validated in animal models, including a non-human primate, and vice versa. The combination of human samples and animal models susceptible to experimental manipulation will promote the translation of clinically relevant data into experimentally testable predictions and promotes the exploitation of therapeutically relevant targets to reverse or halt disease progresssion.