Comprehensive cross-sectional and longitudinal analyses of plasma neurofilament light across FTD spectrum disorders
Tania F. Gendron, Michael G. Heckman, Launia J. White, Austin M. Veire, Otto Pedraza, Alexander R. Burch, Andrea Bozoki, Bradford C. Dickerson, Kimiko Domoto‐Reilly, Tatiana Foroud, Leah K. Forsberg, Douglas Galasko, Nupur Ghoshal, Neill R. Graff‐Radford, Murray Grossman, Hilary W. Heuer, Edward D. Huey, Ging‐Yuek Robin Hsiung, David J. Irwin, Daniel Kaufer, Gabriel C. Léger, Irene Litvan, Joseph C. Masdeu, Mario F. Mendez, Chiadi U. Onyike, Belén Pascual, Aaron Ritter, Erik D. Roberson, Julio C. Rojas, Maria Carmela Tartaglia, Zbigniew K. Wszołek, Howard J. Rosen, Bradley F. Boeve, Adam L. Boxer, Brian S. Appleby, Sami J. Barmada, Yvette Bordelon, Hugo Botha, Danielle Brushaber, David Clark, Giovanni Coppola, Ryan Darby, Katrina L. Devick, Dennis W. Dickson, Kelley Faber, Anne M. Fagan, Julie A. Fields, Ralitza H. Gavrilova, Daniel H. Geschwind, Jill Goldman, Jonathon Graff-Radford, Ian Grant, David T. Jones, Kejal Kantarci, Diana Kerwin, David S. Knopman, John Kornak, Walter K. Kremers, Maria I. Lapid, Argentina Lario Lago, Peter A. Ljubenkov, Diane Lucente, Ian R. Mackenzie, Scott McGinnis, Carly Mester, Bruce L. Miller, Peter Pressman, Rosa Rademakers, Vijay K. Ramanan, Eliana Marisa Ramos, Katherine P. Rankin, Meghana Rao, Katya Rascovsky, Rodolfo Savica, William W. Seeley, Adam M. Staffaroni, Jeremy A. Syrjanen, Jack C. Taylor, Lawren VandeVrede, Sandra Weıntraub, Bonnie Wong, Leonard Petrucelli
Abstract
Frontotemporal dementia (FTD) therapy development is hamstrung by a lack of susceptibility, diagnostic, and prognostic biomarkers. Blood neurofilament light (NfL) shows promise as a biomarker, but studies have largely focused only on core FTD syndromes, often grouping patients with different diagnoses. To expedite the clinical translation of NfL, we avail ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study resources and conduct a comprehensive investigation of plasma NfL across FTD syndromes and in presymptomatic FTD mutation carriers. We find plasma NfL is elevated in all studied syndromes, including mild cases; increases in presymptomatic mutation carriers prior to phenoconversion; and associates with indicators of disease severity. By facilitating the identification of individuals at risk of phenoconversion, and the early diagnosis of FTD, plasma NfL can aid in participant selection for prevention or early treatment trials. Moreover, its prognostic utility would improve patient care, clinical trial efficiency, and treatment outcome estimations.