학술논문

Comprehensive cross-sectional and longitudinal analyses of plasma neurofilament light across FTD spectrum disorders
Document Type
article
Author
Gendron, Tania FHeckman, Michael GWhite, Launia JVeire, Austin MPedraza, OttoBurch, Alexander RBozoki, Andrea CDickerson, Bradford CDomoto-Reilly, KimikoForoud, TatianaForsberg, Leah KGalasko, Douglas RGhoshal, NupurGraff-Radford, Neill RGrossman, MurrayHeuer, Hilary WHuey, Edward DHsiung, Ging-Yuek RIrwin, David JKaufer, Daniel ILeger, Gabriel CLitvan, IreneMasdeu, Joseph CMendez, Mario FOnyike, Chiadi UPascual, BelenRitter, AaronRoberson, Erik DRojas, Julio CTartaglia, Maria CarmelaWszolek, Zbigniew KRosen, HowardBoeve, Bradley FBoxer, Adam Lconsortium, ALLFTDAppleby, Brian SBarmada, SamiBordelon, YvetteBotha, HugoBrushaber, DanielleClark, DavidCoppola, GiovanniDarby, RyanDevick, KatrinaDickson, DennisFaber, KelleyFagan, AnneFields, Julie AGavrilova, RalitzaGeschwind, DanielGoldman, JillGraff-Radford, JonathonGrant, IanJones, David TKantarci, KejalKerwin, DianaKnopman, David SKornak, JohnKremers, WalterLapid, MariaLago, Argentina LarioLjubenkov, PeterLucente, DianeMackenzie, Ian RMcGinnis, ScottMester, CarlyMiller, Bruce LPressman, PeterRademakers, RosaRamanan, Vijay KRamos, E MarisaRankin, Katherine PRao, MeghanaRascovsky, KatyaSavica, RodolfoSeeley, WilliamStaffaroni, Adam MSyrjanen, JeremyTaylor, JackVandeVrede, LawrenWeintraub, SandraWong, BonniePetrucelli, Leonard
Source
Cell Reports Medicine. 3(4)
Subject
Biomedical and Clinical Sciences
Clinical Sciences
Clinical Research
Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD)
Rare Diseases
Dementia
Brain Disorders
Prevention
Acquired Cognitive Impairment
Neurodegenerative
Frontotemporal Dementia (FTD)
4.1 Discovery and preclinical testing of markers and technologies
Detection
screening and diagnosis
Good Health and Well Being
Cross-Sectional Studies
Frontotemporal Dementia
Humans
Intermediate Filaments
Neurofilament Proteins
Pick Disease of the Brain
Syndrome
ALLFTD consortium
Richardson’s syndrome
behavioral variant frontotemporal dementia
biomarker
corticobasal syndrome
neurofilament light
plasma
presymptomatic
primary progressive aphasia
progressive supranuclear palsy
Biomedical and clinical sciences
Language
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.