Risk and Modifying factors in Fronto Temporal Dementia

额颞叶痴呆（FTD）是一种破坏性的老年前痴呆，其特征是额叶的进行性退化，社会和个人行为的改变以及情绪的钝化。高达40%的病例有阳性家族史，这是我们对FTD分子基础的理解取得显著进展的关键。已经确定了7个基因，其中MAPT、GRN和C9Orf72解释了50%的家族性病例，但这些不同的基因如何导致非常相似的临床表型尚不清楚。目前尚无法治愈FTD，治疗的成功与否将取决于单一疗法是否适用于所有患者，或者是否需要针对不同的遗传、临床和病理亚群采取特定的方法。因此，确定疾病发病机制中的所有主要遗传和环境风险和修饰因素至关重要。我们将以现有的遗传和病理知识为起点，利用基于患者遗传和“组学”数据以及相应的动物和细胞模型的多层次方法，解码不同组FTD患者的受影响过程和途径。已确定的网络的生物学意义将在我们的细胞和动物模型中得到验证，并将查明单一ftd亚型特有或所有形式共同的潜在病理机制。研究结果将用于提高我们对有针对性干预的预测质量。

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.