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

ALLFTD consortium

doi:10.1016/j.xcrm.2022.100607

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

ALLFTD consortium

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	100607
Journal	Cell Reports Medicine
Volume	3
Issue number	4
DOIs	https://doi.org/10.1016/j.xcrm.2022.100607
State	Published - Apr 19 2022

Keywords

Richardson's syndrome
behavioral variant frontotemporal dementia
biomarker
corticobasal syndrome
neurofilament light
plasma
presymptomatic
primary progressive aphasia
progressive supranuclear palsy

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.xcrm.2022.100607

Cite this

@article{9658396a8eec4064b3723146e547a7b6,

title = "Comprehensive cross-sectional and longitudinal analyses of plasma neurofilament light across FTD spectrum disorders",

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.",

keywords = "Richardson's syndrome, behavioral variant frontotemporal dementia, biomarker, corticobasal syndrome, neurofilament light, plasma, presymptomatic, primary progressive aphasia, progressive supranuclear palsy",

author = "{ALLFTD consortium} and Gendron, {Tania F.} and Heckman, {Michael G.} and White, {Launia J.} and Veire, {Austin M.} and Otto Pedraza and Burch, {Alexander R.} and Bozoki, {Andrea C.} and Dickerson, {Bradford C.} and Kimiko Domoto-Reilly and Tatiana Foroud and Forsberg, {Leah K.} and Galasko, {Douglas R.} and Nupur Ghoshal and Graff-Radford, {Neill R.} and Murray Grossman and Heuer, {Hilary W.} and Huey, {Edward D.} and Hsiung, {Ging Yuek R.} and Irwin, {David J.} and Kaufer, {Daniel I.} and Leger, {Gabriel C.} and Irene Litvan and Masdeu, {Joseph C.} and Mendez, {Mario F.} and Onyike, {Chiadi U.} and Belen Pascual and Aaron Ritter and Roberson, {Erik D.} and Rojas, {Julio C.} and Tartaglia, {Maria Carmela} and Wszolek, {Zbigniew K.} and Howard Rosen and Boeve, {Bradley F.} and Boxer, {Adam L.} and Appleby, {Brian S.} and Sami Barmada and Yvette Bordelon and Hugo Botha and Danielle Brushaber and Dennis Dickson and Fields, {Julie A.} and Ralitza Gavrilova and Jonathon Graff-Radford and Jones, {David T.} and Kejal Kantarci and Knopman, {David S.} and Walter Kremers and Maria Lapid and Rodolfo Savica and Leonard Petrucelli",

note = "Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = apr,

day = "19",

doi = "10.1016/j.xcrm.2022.100607",

language = "English (US)",

volume = "3",

journal = "Cell Reports Medicine",

issn = "2666-3791",

publisher = "Cell Press",

number = "4",

}

TY - JOUR

T1 - Comprehensive cross-sectional and longitudinal analyses of plasma neurofilament light across FTD spectrum disorders

AU - ALLFTD consortium

AU - Gendron, Tania F.

AU - Heckman, Michael G.

AU - White, Launia J.

AU - Veire, Austin M.

AU - Pedraza, Otto

AU - Burch, Alexander R.

AU - Bozoki, Andrea C.

AU - Dickerson, Bradford C.

AU - Domoto-Reilly, Kimiko

AU - Foroud, Tatiana

AU - Forsberg, Leah K.

AU - Galasko, Douglas R.

AU - Ghoshal, Nupur

AU - Graff-Radford, Neill R.

AU - Grossman, Murray

AU - Heuer, Hilary W.

AU - Huey, Edward D.

AU - Hsiung, Ging Yuek R.

AU - Irwin, David J.

AU - Kaufer, Daniel I.

AU - Leger, Gabriel C.

AU - Litvan, Irene

AU - Masdeu, Joseph C.

AU - Mendez, Mario F.

AU - Onyike, Chiadi U.

AU - Pascual, Belen

AU - Ritter, Aaron

AU - Roberson, Erik D.

AU - Rojas, Julio C.

AU - Tartaglia, Maria Carmela

AU - Wszolek, Zbigniew K.

AU - Rosen, Howard

AU - Boeve, Bradley F.

AU - Boxer, Adam L.

AU - Appleby, Brian S.

AU - Barmada, Sami

AU - Bordelon, Yvette

AU - Botha, Hugo

AU - Brushaber, Danielle

AU - Dickson, Dennis

AU - Fields, Julie A.

AU - Gavrilova, Ralitza

AU - Graff-Radford, Jonathon

AU - Jones, David T.

AU - Kantarci, Kejal

AU - Knopman, David S.

AU - Kremers, Walter

AU - Lapid, Maria

AU - Savica, Rodolfo

AU - Petrucelli, Leonard

PY - 2022/4/19

Y1 - 2022/4/19

N2 - 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.

AB - 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.

KW - Richardson's syndrome

KW - behavioral variant frontotemporal dementia

KW - biomarker

KW - corticobasal syndrome

KW - neurofilament light

KW - plasma

KW - presymptomatic

KW - primary progressive aphasia

KW - progressive supranuclear palsy

UR - http://www.scopus.com/inward/record.url?scp=85128399381&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85128399381&partnerID=8YFLogxK

U2 - 10.1016/j.xcrm.2022.100607

DO - 10.1016/j.xcrm.2022.100607

M3 - Article

C2 - 35492244

AN - SCOPUS:85128399381

SN - 2666-3791

VL - 3

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 4

M1 - 100607

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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