In vivo diagnosis of cognitive impairment base on routine imaging technologies (e.g. magnetic resonance imaging) and observation of clinical syndromes has demonstrated only modest diagnostic accuracy. A biomarker tool is needed that can help in the differential diagnosis of individuals with neurodegenerative disorders with overlapping phenotypes--such as tau-based and TDP-43-based frontotemporal dementia--particularly in the early stages of disease when there is the greatest treatment potential, before there is significant functional disability.There is mounting evidence that TDP-43 and its C-terminal fragment TDP-25 and tau, whose aggregates form the pathological hallmarks of TDP-43 or tau-based frontotemporal dementia respectively, could be exploited as in vivo diagnostic biomarkers.We will complete the design and perform a full clinical validation of a test detection and quantification of TDP-43 isoforms in cerebrospinal fluid. The capacity of this tool to improve diagnostic accuracy will be assessed in a case-control study using well-characterized specimens from our biobank.