Frontotemporal dementia (FTD) is a neurological disorder that clinically presents with behavior and personality changes or language problems. FTD often starts before the age of 65 years. Inspection of tissue of deceased FTD patients has revealed that the disorder is very heterogeneous and that two main subtypes exist. About half of the patients have accumulations of one protein, called tau, and about the other half have accumulations of another protein, called TDP-43. The disease is often misdiagnosed in the early stage, either as a psychiatric disorder, or as a different type of dementia such as Alzheimer's disease (AD). It is therefore of great importance to develop tools that enable an early and accurate diagnosis of FTD and its subtypes. Our aim is to develop such diagnostics tests based on analysis of cerebrospinal fluid. No such diagnostic tests are available yet for discrimination of FTD subtypes or for discriminating FTD patients from controls. For diseases of the brain, no tissue can be obtained from living persons. However, the cerebrospinal fluid is close to the affected tissue and has been proven to be very useful in the diagnosis of Alzheimer's disease. We have build up collections of cerebrospinal fluid and extensive clinical and pathological information of different subtypes of FTD patients. In the current grant, we will apply proteomics technologies. Proteomics is a powerful technology able to analyse up to 1000 proteins in cerebrospinal fluid. This approach will lead to the discovery of novel diagnostic proteins for FTD subtypes and controls. Moreover, it will also lead to novel ideas about the etiology of the disease and more possibilities for treatment development of FTD.