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

doi:10.1016/j.xcrm.2022.100607

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. KauferGabriel 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

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

25 Scopus citations

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

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.xcrm.2022.100607

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Gendron, T. F., Heckman, M. G., White, L. J., Veire, A. M., Pedraza, O., Burch, A. R., Bozoki, A. C., Dickerson, B. C., Domoto-Reilly, K., Foroud, T., Forsberg, L. K., Galasko, D. R., Ghoshal, N., Graff-Radford, N. R., Grossman, M., Heuer, H. W., Huey, E. D., Hsiung, G. Y. R., Irwin, D. J., ... ALLFTD consortium (2022). Comprehensive cross-sectional and longitudinal analyses of plasma neurofilament light across FTD spectrum disorders. Cell Reports Medicine, 3(4), Article 100607. https://doi.org/10.1016/j.xcrm.2022.100607

Gendron, TF, Heckman, MG, White, LJ, Veire, AM, Pedraza, O, Burch, AR, Bozoki, AC, Dickerson, BC, Domoto-Reilly, K, Foroud, T, Forsberg, LK, Galasko, DR, Ghoshal, N, Graff-Radford, NR, Grossman, M, Heuer, HW, Huey, ED, Hsiung, GYR, Irwin, DJ, Kaufer, DI, Leger, GC, Litvan, I, Masdeu, JC, Mendez, MF, Onyike, CU, Pascual, B, Ritter, A, Roberson, ED, Rojas, JC, Tartaglia, MC, Wszolek, ZK, Rosen, H, Boeve, BF, Boxer, AL & ALLFTD consortium 2022, 'Comprehensive cross-sectional and longitudinal analyses of plasma neurofilament light across FTD spectrum disorders', Cell Reports Medicine, vol. 3, no. 4, 100607. https://doi.org/10.1016/j.xcrm.2022.100607

@article{e3804f333b934e9ca9ce72c9e2e1a2db,

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

author = "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 {ALLFTD consortium} and Appleby, {Brian S.} and Sami Barmada and Yvette Bordelon and Hugo Botha and Danielle Brushaber and David Clark and Giovanni Coppola and Ryan Darby and Katrina Devick and Dennis Dickson and Kelley Faber and Anne Fagan and Fields, {Julie A.} and Ralitza Gavrilova and Daniel Geschwind and Jill Goldman",

note = "Funding Information: Data collection and dissemination were supported by the ALLFTD Consortium ( U19AG063911 ; funded by the National Institute on Aging [ NIA ] and the National Institute of Neurological Diseases and Stroke [NINDS]) and the former ARTFL and LEFFTDS Consortia (ARTFL: U54NS092089 , funded by the NINDS and National Center for Advancing Translational Sciences; LEFFTDS: U01AG045390 , funded by the NIA and NINDS ). The manuscript was reviewed by the ALLFTD Executive Committee. Samples from the National Centralized Repository for Alzheimer{\textquoteright}s Disease and Related Dementias (NCRAD), which receives government support under a cooperative agreement grant ( U24AG021886 ) awarded by the NIA , were used in this study. We thank contributors who collected samples used in this study, as well as patients and their families, whose help and participation made this work possible. This work was also supported by the Association for Frontotemporal Degeneration (L.P.) and the NINDS (R35NS097273 [L.P.], P01NS084974 [T.F.G. and L.P.], and P01NS099114 [T.F.G. and L.P.]). Funding Information: Data collection and dissemination were supported by the ALLFTD Consortium (U19AG063911; funded by the National Institute on Aging [NIA] and the National Institute of Neurological Diseases and Stroke [NINDS]) and the former ARTFL and LEFFTDS Consortia (ARTFL: U54NS092089, funded by the NINDS and National Center for Advancing Translational Sciences; LEFFTDS: U01AG045390, funded by the NIA and NINDS). The manuscript was reviewed by the ALLFTD Executive Committee. Samples from the National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD), which receives government support under a cooperative agreement grant (U24AG021886) awarded by the NIA, were used in this study. We thank contributors who collected samples used in this study, as well as patients and their families, whose help and participation made this work possible. This work was also supported by the Association for Frontotemporal Degeneration (L.P.) and the NINDS (R35NS097273 [L.P.], P01NS084974 [T.F.G. and L.P.], and P01NS099114 [T.F.G. and L.P.]). B.F.B. A.L.B. T.F.G. L.P. and H.R. contributed to the conception and/or design of the study. A.C.B. B.C.D. K.D.-R. D.R.G. N.G. N.R.G.-R. M.G. E.D.H. G.-Y.R.H. D.J.I. D.I.K. G.C.L. I.L. J.C.M. M.F.M. C.U.O. B.P. A.R. E.D.R. J.C.R. M.C.T. and Z.K.W. contributed through patient evaluations, collecting patient samples, and/or clinical data. L.K.F. and H.W.H. contributed to the study design and clinical data. T.F. contributed through protocol development and management and biospecimen collection. T.F.G. measured NfL concentrations, and A.R.B. assisted with sample processing. O.P. conducted patient evaluations and provided guidance on the selection of disease indicators. Statistical analyses were performed by M.G.H. and L.J.W. Literature review was undertaken by T.F.G. and A.M.V. The manuscript was written by T.F.G. and M.G.H. and was reviewed by all authors. A.C.B. is site PI for the Alector INFRONT-3 trial. A.L.B. receives research support from NIH (R01AG038791, R01AG073482, and U24AG057437), Rainwater Charitable Foundation, Association for Frontotemporal Degeneration, Bluefield Project to Cure Frontotemporal Dementia, Alzheimer's Drug Discovery Foundation, and the Alzheimer's Association. He has served as a consultant for Alector, AGTC, Arkuda, Arvinas, AZTherapies, GSK, Oligomerix, Ono, Roche, Samumed, Stealth, Third Rock, Transposon, TrueBinding, and Wave and received research support from Biogen, Eisai, and Regeneron. B.F.B. has served as an investigator for clinical trials sponsored by Biogen, Alector, and EIP Pharma. He receives royalties from a published book entitled Behavioral Neurology of Dementia (Cambridge Medicine, 2009, 2017), serves on the Tau Consortium Scientific Advisory Board, and receives research support from the NIH. B.C.D. consults for Acadia, Arkuda, Axovant, Lilly, Biogen, Merck, Novartis, and Wave LifeSciences; has Elsevier editorial duties with payment (Neuroimage: Clinical and Cortex); and receives royalties from Oxford University Press and Cambridge University Press. K.D.-R. has research funding from Biogen and Lawson Health Research Institute and receives consultant fees from Biogen and educational fees from MedBridge. D.R.G. consults for Biogen, Fujirebio, and Amprion and is on the DSMB for Cognition Therapeutics. M.G. is participating in treatment trials sponsored by Alector, Prevail, and Passage Bio and is a consultant to Takeda, Passage Bio, and Biogen. N.G. has or is participating in clinical trials of anti-dementia drugs sponsored by Bristol Myers Squibb, Lilly/Avid Radiopharmaceuticals, Janssen, Novartis, Pfizer, and Wyeth. N.R.G.-R. has taken part in multicenter studies funded by Biogen, AbbVie, and Lilly. G.-Y.R.H. has received research support from Anavax, Biogen, and Roche. I.L. received support from Roche, Abbvie, Biogen, EIP-Pharma, and Biohaven Pharmaceuticals; was member of a Lundbeck Advisory Board; and receives salary from the University of California, San Diego and as Chief Editor of Frontiers in Neurology. J.C.M. participates on a speaker forum for Biogen and receives research support from Biogen, Eisai, Eli Lilly, Green Valley, and Novartis. C.U.O. is a consultant with Alector and Acadia and receives research funding from Alector. L.P. is a consultant for Expansion Therapeutics. E.D.R. receives funding from NIH, Alzheimer's Drug Discovery Foundation, Bluefield Project, and Alector; consults for Biogen, AVROBIO, and AGTC; and owns intellectual property related to tau. J.C.R. is a site PI for Eli Lilly and Eisai clinical trials and receives research support from NIH K23AG059888. M.C.T. participates in clinical trials with Biogen, Avanex, UCB, and Janssen. Z.K.W. is supported by the NIH/NIA and NIH/NINDS (1U19AG063911, FAIN: U19AG063911), Mayo Clinic Center for Regenerative Medicine, Mayo Clinic in Florida Focused Research Team Program, the gifts from The Sol Goldman Charitable Trust, the Donald G. and Jodi P. Heeringa Family, the Haworth Family Professorship in Neurodegenerative Diseases fund, and The Albertson Parkinson's Research Foundation. He serves as PI or co-PI on Biohaven Pharmaceuticals, Inc. (BHV4157-206 and BHV3241-301); Neuraly, Inc. (NLY01-PD-1); and Vigil Neuroscience, Inc. (VGL101?01.001) grants. He serves as co-PI of the Mayo Clinic APDA Center for Advanced Research and as an external advisory board member for Vigil Neuroscience, Inc. All other authors report no competing interests. 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 - 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 - ALLFTD consortium

AU - Appleby, Brian S.

AU - Barmada, Sami

AU - Bordelon, Yvette

AU - Botha, Hugo

AU - Brushaber, Danielle

AU - Clark, David

AU - Coppola, Giovanni

AU - Darby, Ryan

AU - Devick, Katrina

AU - Dickson, Dennis

AU - Faber, Kelley

AU - Fagan, Anne

AU - Fields, Julie A.

AU - Gavrilova, Ralitza

AU - Geschwind, Daniel

AU - Goldman, Jill

N1 - Funding Information: Data collection and dissemination were supported by the ALLFTD Consortium ( U19AG063911 ; funded by the National Institute on Aging [ NIA ] and the National Institute of Neurological Diseases and Stroke [NINDS]) and the former ARTFL and LEFFTDS Consortia (ARTFL: U54NS092089 , funded by the NINDS and National Center for Advancing Translational Sciences; LEFFTDS: U01AG045390 , funded by the NIA and NINDS ). The manuscript was reviewed by the ALLFTD Executive Committee. Samples from the National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD), which receives government support under a cooperative agreement grant ( U24AG021886 ) awarded by the NIA , were used in this study. We thank contributors who collected samples used in this study, as well as patients and their families, whose help and participation made this work possible. This work was also supported by the Association for Frontotemporal Degeneration (L.P.) and the NINDS (R35NS097273 [L.P.], P01NS084974 [T.F.G. and L.P.], and P01NS099114 [T.F.G. and L.P.]). Funding Information: Data collection and dissemination were supported by the ALLFTD Consortium (U19AG063911; funded by the National Institute on Aging [NIA] and the National Institute of Neurological Diseases and Stroke [NINDS]) and the former ARTFL and LEFFTDS Consortia (ARTFL: U54NS092089, funded by the NINDS and National Center for Advancing Translational Sciences; LEFFTDS: U01AG045390, funded by the NIA and NINDS). The manuscript was reviewed by the ALLFTD Executive Committee. Samples from the National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD), which receives government support under a cooperative agreement grant (U24AG021886) awarded by the NIA, were used in this study. We thank contributors who collected samples used in this study, as well as patients and their families, whose help and participation made this work possible. This work was also supported by the Association for Frontotemporal Degeneration (L.P.) and the NINDS (R35NS097273 [L.P.], P01NS084974 [T.F.G. and L.P.], and P01NS099114 [T.F.G. and L.P.]). B.F.B. A.L.B. T.F.G. L.P. and H.R. contributed to the conception and/or design of the study. A.C.B. B.C.D. K.D.-R. D.R.G. N.G. N.R.G.-R. M.G. E.D.H. G.-Y.R.H. D.J.I. D.I.K. G.C.L. I.L. J.C.M. M.F.M. C.U.O. B.P. A.R. E.D.R. J.C.R. M.C.T. and Z.K.W. contributed through patient evaluations, collecting patient samples, and/or clinical data. L.K.F. and H.W.H. contributed to the study design and clinical data. T.F. contributed through protocol development and management and biospecimen collection. T.F.G. measured NfL concentrations, and A.R.B. assisted with sample processing. O.P. conducted patient evaluations and provided guidance on the selection of disease indicators. Statistical analyses were performed by M.G.H. and L.J.W. Literature review was undertaken by T.F.G. and A.M.V. The manuscript was written by T.F.G. and M.G.H. and was reviewed by all authors. A.C.B. is site PI for the Alector INFRONT-3 trial. A.L.B. receives research support from NIH (R01AG038791, R01AG073482, and U24AG057437), Rainwater Charitable Foundation, Association for Frontotemporal Degeneration, Bluefield Project to Cure Frontotemporal Dementia, Alzheimer's Drug Discovery Foundation, and the Alzheimer's Association. He has served as a consultant for Alector, AGTC, Arkuda, Arvinas, AZTherapies, GSK, Oligomerix, Ono, Roche, Samumed, Stealth, Third Rock, Transposon, TrueBinding, and Wave and received research support from Biogen, Eisai, and Regeneron. B.F.B. has served as an investigator for clinical trials sponsored by Biogen, Alector, and EIP Pharma. He receives royalties from a published book entitled Behavioral Neurology of Dementia (Cambridge Medicine, 2009, 2017), serves on the Tau Consortium Scientific Advisory Board, and receives research support from the NIH. B.C.D. consults for Acadia, Arkuda, Axovant, Lilly, Biogen, Merck, Novartis, and Wave LifeSciences; has Elsevier editorial duties with payment (Neuroimage: Clinical and Cortex); and receives royalties from Oxford University Press and Cambridge University Press. K.D.-R. has research funding from Biogen and Lawson Health Research Institute and receives consultant fees from Biogen and educational fees from MedBridge. D.R.G. consults for Biogen, Fujirebio, and Amprion and is on the DSMB for Cognition Therapeutics. M.G. is participating in treatment trials sponsored by Alector, Prevail, and Passage Bio and is a consultant to Takeda, Passage Bio, and Biogen. N.G. has or is participating in clinical trials of anti-dementia drugs sponsored by Bristol Myers Squibb, Lilly/Avid Radiopharmaceuticals, Janssen, Novartis, Pfizer, and Wyeth. N.R.G.-R. has taken part in multicenter studies funded by Biogen, AbbVie, and Lilly. G.-Y.R.H. has received research support from Anavax, Biogen, and Roche. I.L. received support from Roche, Abbvie, Biogen, EIP-Pharma, and Biohaven Pharmaceuticals; was member of a Lundbeck Advisory Board; and receives salary from the University of California, San Diego and as Chief Editor of Frontiers in Neurology. J.C.M. participates on a speaker forum for Biogen and receives research support from Biogen, Eisai, Eli Lilly, Green Valley, and Novartis. C.U.O. is a consultant with Alector and Acadia and receives research funding from Alector. L.P. is a consultant for Expansion Therapeutics. E.D.R. receives funding from NIH, Alzheimer's Drug Discovery Foundation, Bluefield Project, and Alector; consults for Biogen, AVROBIO, and AGTC; and owns intellectual property related to tau. J.C.R. is a site PI for Eli Lilly and Eisai clinical trials and receives research support from NIH K23AG059888. M.C.T. participates in clinical trials with Biogen, Avanex, UCB, and Janssen. Z.K.W. is supported by the NIH/NIA and NIH/NINDS (1U19AG063911, FAIN: U19AG063911), Mayo Clinic Center for Regenerative Medicine, Mayo Clinic in Florida Focused Research Team Program, the gifts from The Sol Goldman Charitable Trust, the Donald G. and Jodi P. Heeringa Family, the Haworth Family Professorship in Neurodegenerative Diseases fund, and The Albertson Parkinson's Research Foundation. He serves as PI or co-PI on Biohaven Pharmaceuticals, Inc. (BHV4157-206 and BHV3241-301); Neuraly, Inc. (NLY01-PD-1); and Vigil Neuroscience, Inc. (VGL101?01.001) grants. He serves as co-PI of the Mayo Clinic APDA Center for Advanced Research and as an external advisory board member for Vigil Neuroscience, Inc. All other authors report no competing interests. Publisher Copyright: © 2022 The Author(s)

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

KW - Cross-Sectional Studies

KW - Frontotemporal Dementia/diagnosis

KW - Humans

KW - Pick Disease of the Brain

KW - Neurofilament Proteins/genetics

KW - Syndrome

KW - Intermediate Filaments

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

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Keywords

ASJC Scopus subject areas

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