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 C Bozoki; Bradford C Dickerson; Kimiko Domoto-Reilly; Tatiana Foroud; Leah K Forsberg; Douglas R Galasko; Nupur Ghoshal; Neill R Graff-Radford; Murray Grossman; Hilary W Heuer; Edward D Huey; Ging-Yuek R Hsiung; David J Irwin; Daniel I Kaufer; Gabriel C Leger; Irene Litvan; Joseph C Masdeu; Mario F Mendez; Chiadi U Onyike; Belen Pascual; Aaron Ritter; Erik D Roberson; Julio C Rojas; Maria Carmela Tartaglia; Zbigniew K Wszolek; Howard Rosen; Bradley F Boeve; Adam L Boxer; ALLFTD consortium; Leonard Petrucelli

doi:10.1016/j.xcrm.2022.100607

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

Cell Rep Med. 2022 Apr 19;3(4):100607. doi: 10.1016/j.xcrm.2022.100607.

Authors

Tania F Gendron¹, Michael G Heckman², Launia J White², Austin M Veire³, Otto Pedraza⁴, Alexander R Burch⁵, Andrea C Bozoki⁶, Bradford C Dickerson⁷, Kimiko Domoto-Reilly⁸, Tatiana Foroud⁹, Leah K Forsberg¹⁰, Douglas R Galasko¹¹, Nupur Ghoshal¹², Neill R Graff-Radford⁵, Murray Grossman¹³, Hilary W Heuer¹⁴, Edward D Huey¹⁵, Ging-Yuek R Hsiung¹⁶, David J Irwin¹⁷, Daniel I Kaufer⁶, Gabriel C Leger¹¹, Irene Litvan¹¹, Joseph C Masdeu¹⁸, Mario F Mendez¹⁹, Chiadi U Onyike²⁰, Belen Pascual¹⁸, Aaron Ritter²¹, Erik D Roberson²², Julio C Rojas¹⁴, Maria Carmela Tartaglia²³, Zbigniew K Wszolek⁵, Howard Rosen¹⁴, Bradley F Boeve¹⁰, Adam L Boxer¹⁴; ALLFTD consortium; Leonard Petrucelli²⁴

Collaborators

ALLFTD consortium:
Brian S Appleby, Sami Barmada, Yvette Bordelon, Hugo Botha, Danielle Brushaber, David Clark, Giovanni Coppola, Ryan Darby, Katrina Devick, Dennis Dickson, Kelley Faber, Anne Fagan, Julie A Fields, Ralitza Gavrilova, Daniel Geschwind, Jill Goldman, Jonathon Graff-Radford, Ian Grant, David T Jones, Kejal Kantarci, Diana Kerwin, David S Knopman, John Kornak, Walter Kremers, Maria Lapid, Argentina Lario Lago, Peter Ljubenkov, Diane Lucente, Ian R Mackenzie, Scott McGinnis, Carly Mester, Bruce L Miller, Peter Pressman, Rosa Rademakers, Vijay K Ramanan, E Marisa Ramos, Katherine P Rankin, Meghana Rao, Katya Rascovsky, Rodolfo Savica, William Seeley, Adam M Staffaroni, Jeremy Syrjanen, Jack Taylor, Lawren VandeVrede, Sandra Weintraub, Bonnie Wong

Affiliations

¹ Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA; Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Jacksonville, FL 32224, USA. Electronic address: Gendron.Tania@mayo.edu.
² Division of Clinical Trials and Biostatistics, Mayo Clinic, Jacksonville, FL 32224, USA.
³ Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
⁴ Department of Psychiatry & Psychology, Mayo Clinic, Jacksonville, FL 32224, USA.
⁵ Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA.
⁶ Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁷ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
⁸ Department of Neurology, University of Washington, Seattle, WA 98104, USA.
⁹ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
¹⁰ Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
¹¹ Parkinson and Other Movement Disorder Center, Department of Neuroscience, University of California, San Diego, La Jolla, CA 92037, USA.
¹² Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA.
¹³ Department of Neurology, University of Pennsylvania, Philadelphia, PA 19104, USA.
¹⁴ Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
¹⁵ Department of Psychiatry, Taub Institute, Columbia University, New York, NY 10032, USA; Department of Neurology, Taub Institute, Columbia University, New York, NY 10032, USA.
¹⁶ Centre for Brain Health, Department of Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
¹⁷ Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
¹⁸ Nantz National Alzheimer Center, Stanley H. Appel Department of Neurology, Houston Methodist Research Institute, Weill Cornell Medicine, Houston, TX 77030, USA.
¹⁹ Department of Neurology, University of California at Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, Los Angeles, CA 90095, USA.
²⁰ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD 21287, USA.
²¹ Neurological Institute, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV 89106, USA.
²² Center for Neurodegeneration and Experimental Therapeutics, Alzheimer's Disease Center, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
²³ Krembil Brain Institute, Tanz Centre for Research in Neurodegenerative Diseases, Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
²⁴ Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA; Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Jacksonville, FL 32224, USA. Electronic address: Petrucelli.Leonard@mayo.edu.

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.

Trial registration: ClinicalTrials.gov NCT02372773 NCT02365922.

Keywords: Richardson’s syndrome; behavioral variant frontotemporal dementia; biomarker; corticobasal syndrome; neurofilament light; plasma; presymptomatic; primary progressive aphasia; progressive supranuclear palsy.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cross-Sectional Studies
Frontotemporal Dementia* / diagnosis
Humans
Intermediate Filaments
Neurofilament Proteins / genetics
Pick Disease of the Brain*
Syndrome

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

Authors

Collaborators

Affiliations

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding