Frontotemporal lobar degeneration (FTLD) is a fatal, degenerative brain disease that is a common cause of dementia in people under the age of 60. Often striking people in their prime, FTD is characterized by a progressive degeneration of the frontal portions of the brain, the regions responsible for language and behavior. FTLD patients may lose the ability to behave appropriately, make judgments, communicate, and carry out daily activities. There are no effective treatments, however several investigational agents are in clinical development.

 Approximately 25% of FTLD cases are familial (f-FTLD) and due to autosomal dominant mutations in one of three genes: C9orf72, GRN or MAPT. Many of the new therapies entering the clinic directly target one of these genetic causes and raise the possibility that disease could be prevented if an efficacious therapy was initiated prior to the onset of symptoms. The goal of this proposal is to qualify plasma neurofilament light chain (NfL) as an endpoint for f-FTLD prevention trials, so that it can indicate therapeutic efficacy prior to the onset of symptoms.

 We have assembled a pre-competitive, public-private partnership, called the Neurofilament Surveillance Project (NSP), involving patient advocacy groups, academic FTLD researchers and pharmaceutical companies. The NSP leverages the well-established, 18-site NIH-funded ARTFL/LEFFTDS clinical trial research network to greatly facilitate study enrollment, and, most importantly, to enable correlations with clinical measures such as brain volume and functional assessments. 320 participants will donate blood at home via visits from traveling nurses four times a year for three years (3840 samples total), thus enabling us to observe peripheral NfL levels longitudinally during disease onset and progression. Plasma NfL will be assessed in association with rigorous clinical and neuroimaging data available through ARTFL/LEFFTDS, making this prospective data set uniquely valuable to understand NfL as a prognostic biomarker in genetic FTD.