Frontotemporal dementia (FTD), the second most common cause of dementia that currently lacks a blood test for early diagnosis. This is an important issue as early diagnosis will facilitate early treatment, resulting in greater benefit for patients. While the onset of illness is cannot be clearly defined, it is thought patients with FTD shows a period with limited signs/symptoms before appearance of clinical symptoms. These presymptomatic stages may represent a critical window for early diagnosis. One potential way to identify this early phase of the illness to develop a blood test that enables the physician to monitor changes in the brain of FTD patients. Over the past decades, the gene encoding an disease protein called TDP-43 causes about 50% of all cases of FTD and studies support the idea that corrupted TDP-43 function is the culprit for this type of FTD patients. We recently developed a potential blood or cerebrospinal fluid (CSF) test to monitor the corruption of TDP-43 function by detection of a protein called “cryptic HDGFL2”.We have used such diagnostic test in a related human disease called motor neuron disease (or ALS) and showed that corruption of TDP-43 function happens prior to symptom onset, during the prodromal phase in carriers with genetic cause of the disease (called C9ORF72 repeat expansion). Based on this observation, we plan to study a large cohort of FTD patients (called GENFI cohort) in which blood or CSF draws from presymptomatic and symptomatic stage of disease are already available. We believe that this potential diagnostic test would be useful to determine how early the corruption of TDP-43 function occurs in FTD patients, providing an unprecedented opportunity for early diagnosis and treatment for this devastating illness of the elderly.