Evidence map›Paper›PMID 40075459›Full record

ArticleMolecular neurodegeneration2025

Comprehensive cross-sectional and longitudinal comparisons of plasma glial fibrillary acidic protein and neurofilament light across FTD spectrum disorders.

Udit Sheth, Linn Öijerstedt, Michael G Heckman, Launia J White, Hilary W Heuer, Argentina Lario Lago, Leah K Forsberg, Kelley M Faber, Tatiana M Foroud, Rosa Rademakers and 32 more

Abstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular neurodegeneration, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Moderating effects of plasma glial fibrillary acidic protein along the Alzheimer's disease continuum.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  13. Article
  14. Review
  15. Article
  16. Real-world utility of plasma GFAP and NfL in early-onset AD and FTD.Alzheimer's & dementia (Amsterdam, Netherlands)
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

42 authors.

Udit ShethDepartment of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
Linn ÖijerstedtDepartment of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
Michael G HeckmanDivision of Clinical Trials and Biostatistics, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
Launia J WhiteDivision of Clinical Trials and Biostatistics, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
Hilary W HeuerMemory and Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 91358, USA.
Argentina Lario LagoMemory and Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 91358, USA.
Leah K ForsbergDepartment of Neurology, Mayo Clinic, 200 First St, SW, Rochester, MN, 55905, USA.
Kelley M FaberDepartment of Medical and Molecular Genetics, The National Centralized Repository for Alzheimer's Disease and Related Dementias, 351 W. 10Th St TK-217, Indianapolis, IN, 46202, USA.
Tatiana M ForoudDepartment of Medical and Molecular Genetics, The National Centralized Repository for Alzheimer's Disease and Related Dementias, 351 W. 10Th St TK-217, Indianapolis, IN, 46202, USA.
Rosa RademakersDepartment of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
Eliana Marisa RamosDepartment of Neurology, David Geffen School of Medicine, University of California Los Angeles, Reed Neurological Research Center, 710 Westwood Plaza, Los Angeles, CA, 90095, USA.
Brian S ApplebyDepartment of Neurology, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH, 44106, USA.
Andrea C BozokiDepartment of Neurology, University of North Carolina, 170 Manning Dr, Chapel Hill, NC, 27599, USA.
R Ryan DarbyDepartment of Neurology, Vanderbilt University, 1161 21St Ave S, Nashville, TN, 37212, USA.
Bradford C DickersonDepartment of Neurology, Frontotemporal Disorders Unit, Massachusetts General Hospital and Harvard Medical School, 149 13th St, Boston, MA, 02129, USA.
Kimiko Domoto-ReillyDepartment of Neurology, University of Washington, 1959 NE Pacific St, Seattle, WA, 98195-6465, USA.
Douglas R GalaskoDepartment of Neurosciences, University of California, 9500 Gilman Drive, La Jolla, CA, 92037-0948, USA.
Nupur GhoshalDepartments of Neurology and Psychiatry, Washington University School of Medicine, Washington University, 660 South Euclid, St. Louis, MO, 63110, USA.
Neill R Graff-RadfordDepartment of Neurology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
Ian M GrantDepartment of Neurology, Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern Feinberg School of Medicine, 300 E. Superior, Tarry 8-715, Chicago, IL, 60610, USA.
Chadwick M HalesCenter for Neurodegenerative Disease, Department of Neurology, Emory University School of Medicine and Emory, 12 Executive Park Drive, Atlanta, GA, 30329, USA.
Ging-Yuek Robin HsiungDivision of Neurology, University of British Columbia, S151-2211 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada.
Edward D HueyDepartment of Psychiatry and Human Behavior, Alpert Medical School of Brown University, 345 Blackstone Boulevard, Providence, RI, 02906, USA.
David IrwinDepartment of Neurology and Penn Frontotemporal Degeneration Center, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce St, Philadelphia, PA, 19104, USA.
Justin Y KwanDisorders and Stroke, National Institute of Neurological, National Institutes of Health, 10 Center Drive, Bethesda, MD, 20892, USA.
Irene LitvanDepartment of Neurosciences, University of California, 9452 Medical Center Drive, La Jolla, CA, 92037, USA.
Ian R MackenzieDepartment of Pathology and Laboratory Medicine, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada.
Joseph C MasdeuDepartment of Neurology, Houston Methodist Neurological Institute, Weill Cornell Medicine, 6560 Fannin St, Houston, TX, 77030, USA.
Mario F MendezDepartment of Neurology, David Geffen School of Medicine, University of California Los Angeles, Reed Neurological Research Center, 710 Westwood Plaza, Los Angeles, CA, 90095, USA.
Chiadi U OnyikeDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD, 21287, USA.
Belen PascualDepartment of Neurology, Houston Methodist Neurological Institute, Weill Cornell Medicine, 6560 Fannin St, Houston, TX, 77030, USA.
Peter S PressmanDepartment of Neurology, University of Colorado School of Medicine, 12631 East 17Th Avenue, Aurora, CO, 80045, USA.
Erik D RobersonDepartment of Neurology, University of Alabama at Birmingham, 1825 University Blvd, Birmingham, AL, 35233, USA.
Allison SnyderDisorders and Stroke, National Institute of Neurological, National Institutes of Health, 10 Center Drive, Bethesda, MD, 20892, USA.
M Carmela TartagliaDivision of Neurology, Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen's Park Crescent West, Third Floor, Toronto, ON, M5S 3H2, Canada.
William W SeeleyMemory and Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 91358, USA.
Dennis W DicksonDepartment of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
Howard J RosenMemory and Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 91358, USA.
Bradley F BoeveDepartment of Neurology, Mayo Clinic, 200 First St, SW, Rochester, MN, 55905, USA.
Adam L BoxerMemory and Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 91358, USA.
Leonard PetrucelliDepartment of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
Tania F GendronDepartment of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA. Gendron.Tania@mayo.edu.ORCID 0000-0002-7335-2627

Funding

Technology and Remote Assessment CoreU19AG063911 · NIA · MAYO CLINIC ROCHESTER · PI ADAM L. BOXER, Bradley F Boeve · 2019 to 2026
$120.9M
National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8M
TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2M
Research Education ComponentP30AG062422 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jennifer S Yokoyama · 2019 to 2026
$36.9M
UCSD Shiley-Marcos Alzheimer's Disease Research Center P30P30AG062429 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DOUGLAS R GALASKO · 2019 to 2026
$34.9M
Research Education ComponentP30AG062677 · NIA · MAYO CLINIC ROCHESTER · PI KEJAL KANTARCI · 2019 to 2026
$33.5M
University of Washington Alzheimer's Disease Research CenterP30AG066509 · NIA · UNIVERSITY OF WASHINGTON · PI Amanda D. Boyd · 2020 to 2026
$29.0M
PrPSc SPECIFIC INTERACTION WITH NOVEL PrP-Fc FUSION PROTEINSP50AG023501 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MILLER, BRUCE L · 2004 to 2018
$27.1M
Project 3: Neuropathology of the multi-proteinopathy of c9FTD/ALS.P01NS084974 · NINDS · MAYO CLINIC JACKSONVILLE · PI PETRUCELLI, LEONARD · 2014 to 2024
$17.6M
Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS)U01AG045390 · NIA · MAYO CLINIC ROCHESTER · PI BOEVE, BRADLEY F, ROSEN, HOWARD J · 2014 to 2018
$16.9M
Expanding insights into FTD disease mechanismsR35NS097273 · NINDS · MAYO CLINIC JACKSONVILLE · PI PETRUCELLI, LEONARD · 2017 to 2024
$10.6M
Validation of r(G4C2)exp-binding small molecules in vivo and c9FTD/ALS biomarker developmentP01NS099114 · NINDS · UNIVERSITY OF FLORIDA · PI DISNEY, MATTHEW D · 2017 to 2021
$6.5M
NIA NIH HHS K24 AG045333NIA NIH HHS K24AG045333NIA NIH HHS P01 AG019724NIA NIH HHS P01AG019724NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG062429NIA NIH HHS P30 AG062677NIA NIH HHS P30AG062677NIA NIH HHS P30 AG066509NIA NIH HHS P30AG066509NIA NIH HHS P50 AG023501NIA NIH HHS U01 AG045390NIA NIH HHS U01AG045390NIA NIH HHS U19 AG063911NIA NIH HHS U19AG063911NIA NIH HHS U24 AG021886NIA NIH HHS U24AG021886NINDS NIH HHS P01 NS084974NINDS NIH HHS P01NS084974NINDS NIH HHS P01 NS099114NINDS NIH HHS P01NS099114NINDS NIH HHS R35 NS097273NINDS NIH HHS R35NS097273NINDS NIH HHS U54 NS092089NINDS NIH HHS U54NS092089
6 · The paper itself

Abstract

backgroundTherapeutic development for frontotemporal dementia (FTD) is hindered by the lack of biomarkers that inform susceptibility/risk, prognosis, and the underlying causative pathology. Blood glial fibrillary acidic protein (GFAP) has garnered attention as a FTD biomarker. However, investigations of GFAP in FTD have been hampered by symptomatic and histopathologic heterogeneity and small cohort sizes contributing to inconsistent findings. Therefore, we evaluated plasma GFAP as a FTD biomarker and compared its performance to that of neurofilament light (NfL) protein, a leading FTD biomarker.

methodsWe availed ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study resources to conduct a comprehensive cross-sectional and longitudinal examination of the susceptibility/risk, prognostic, and predictive performance of GFAP and NfL in the largest series of well-characterized presymptomatic FTD mutation carriers and participants with sporadic or familial FTD syndromes. Utilizing single molecule array technology, we measured GFAP and NfL in plasma from 161 controls, 127 presymptomatic mutation carriers, 702 participants with a FTD syndrome, and 67 participants with mild behavioral and/or cognitive changes. We used multivariable linear regression and Cox proportional hazard models adjusted for co-variates to examine the biomarker utility of baseline GFAP and NfL concentrations or their rates of change.

resultsCompared to controls, GFAP and NfL were elevated in each FTD syndrome but GFAP, unlike NfL, poorly discriminated controls from participants with mild symptoms. Similarly, both baseline GFAP and NfL were higher in presymptomatic mutation carriers who later phenoconverted, but NfL better distinguished non-converters from phenoconverters. We additionally observed that GFAP and NfL were associated with disease severity indicators and survival, but NfL far outperformed GFAP. Nevertheless, we validated findings that the GFAP/NfL ratio may discriminate frontotemporal lobar degeneration with tau versus TDP-43 pathology.

conclusionsOur head-to-head comparison of plasma GFAP and NfL as biomarkers for FTD indicate that NfL consistently outmatched GFAP as a prognostic and predictive biomarker for participants with a FTD syndrome, and as a susceptibility/risk biomarker for people at genetic risk of FTD. Our findings underscore the need to include leading biomarkers in investigations evaluating new biomarkers if the field is to fully ascertain their performance and clinical value.

Indexed as

Frontotemporal DementiaGlial Fibrillary Acidic ProteinNeurofilament ProteinsAdultAgedBiomarkersCross-Sectional StudiesFemaleHumansLongitudinal StudiesMaleMiddle AgedBiomarkersGFAP protein, humanGlial Fibrillary Acidic Proteinneurofilament protein LNeurofilament ProteinsBehavioral variant frontotemporal dementiaBiofluidBiomarkerCorticobasal syndromeGlial fibrillary acidic proteinNeurofilament lightPlasmaPresymptomaticPrimary progressive aphasiaProgressive supranuclear palsy-Richardson’s syndrome

Identifiers

PMID40075459
PMCPMC11905702

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.