Comprehensive cross-sectional and longitudinal analyses of plasma neurofilament light across FTD spectrum disorders

• Published in: Cell reports. Medicine Vol. 3; no. 4; p. 100607
• Main Authors: Gendron, Tania F., Heckman, Michael G., White, Launia J., Veire, Austin M., Pedraza, Otto, Burch, Alexander R., Bozoki, Andrea C., Dickerson, Bradford C., Domoto-Reilly, Kimiko, Foroud, Tatiana, Forsberg, Leah K., Galasko, Douglas R., Ghoshal, Nupur, Graff-Radford, Neill R., Grossman, Murray, Heuer, Hilary W., Huey, Edward D., Hsiung, Ging-Yuek R., Irwin, David J., Kaufer, Daniel I., Leger, Gabriel C., Litvan, Irene, Masdeu, Joseph C., Mendez, Mario F., Onyike, Chiadi U., Pascual, Belen, Ritter, Aaron, Roberson, Erik D., Rojas, Julio C., Tartaglia, Maria Carmela, Wszolek, Zbigniew K., Rosen, Howard, Boeve, Bradley F., Boxer, Adam L., Appleby, Brian S., Barmada, Sami, Bordelon, Yvette, Botha, Hugo, Brushaber, Danielle, Clark, David, Coppola, Giovanni, Darby, Ryan, Devick, Katrina, Dickson, Dennis, Faber, Kelley, Fagan, Anne, Fields, Julie A., Gavrilova, Ralitza, Geschwind, Daniel, Goldman, Jill, Graff-Radford, Jonathon, Grant, Ian, Jones, David T., Kantarci, Kejal, Kerwin, Diana, Knopman, David S., Kornak, John, Kremers, Walter, Lapid, Maria, Lago, Argentina Lario, Ljubenkov, Peter, Lucente, Diane, Mackenzie, Ian R., McGinnis, Scott, Mester, Carly, Miller, Bruce L., Pressman, Peter, Rademakers, Rosa, Ramanan, Vijay K., Ramos, E. Marisa, Rankin, Katherine P., Rao, Meghana, Rascovsky, Katya, Savica, Rodolfo, Seeley, William, Staffaroni, Adam M., Syrjanen, Jeremy, Taylor, Jack, VandeVrede, Lawren, Weintraub, Sandra, Wong, Bonnie, Petrucelli, Leonard
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.04.2022; Elsevier
• Subjects: Advanced Basic Science; behavioral variant frontotemporal dementia; biomarker; corticobasal syndrome; Cross-Sectional Studies; Frontotemporal Dementia - diagnosis; Humans; Intermediate Filaments; neurofilament light; Neurofilament Proteins - genetics; Pick Disease of the Brain; plasma; presymptomatic; primary progressive aphasia; progressive supranuclear palsy; Richardson’s syndrome; Syndrome; behavioral variant frontotemporal dementia; presymptomatic; biomarker; corticobasal syndrome; neurofilament light; plasma; primary progressive aphasia; progressive supranuclear palsy; Richardson’s syndrome
• ISSN: 2666-3791; 2666-3791
• DOI: 10.1016/j.xcrm.2022.100607

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. [Display omitted] •Plasma NfL levels increase prior to frontotemporal dementia (FTD) symptom onset•Plasma NfL can facilitate an earlier FTD diagnosis•Plasma NfL levels associate with clinical indicators of FTD disease severity•Plasma NfL shows promise as a susceptibility and prognostic biomarker for FTD Gendron et al. show that plasma neurofilament light (NfL) increases before symptom onset in individuals with a genetic risk of frontotemporal dementia (FTD) and associates with clinical indicators of disease severity. Plasma NfL thus holds promise as a susceptibility and prognostic biomarker that can improve patient care and FTD treatment development.