Risk and Modifying factors in Fronto Temporal Dementia

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Fronto Temporal Dementia (FTD) is a devastating pre-senile dementia characterized by the progressivedeterioration of the frontal lobe and changes in social and personal behaviour and blunting of emotions.Up to 40% of cases have a positive family history and this has been the key to the remarkable progressin our understanding of the molecular basis of FTD. Seven genes have been identified of which MAPT, GRN and C9Orf72 explain >50% of familial cases, but how these different genes lead to a very similar clinical phenotype is unknown. There is no cure for FTD and success of therapy will depend on whether a single therapy can be applied to all patients or if specific approaches are needed for the distinct genetic, clinical and pathological subgroups. Therefore it is essential to identify all major genetic and environmental risk and modifying factors in the pathogenesis of the disease.We will use existing genetic and pathological knowledge as a starting point to decode affectedprocesses and pathways in different groups of patients with FTD using a multi level approach based on genetic and "omics" data from patients and corresponding animal and cellular models. The biological significance of identified networks will be validated in our cellular and animal models and will pinpoint potential pathomechanisms that are specific to a single FTD-subtype or common to all forms. The results will be utilized to improve the quality of our predictions towards targeted intervention.