ArticleAnnals of clinical and translational neurology2021
Brain volumetric deficits in MAPT mutation carriers: a multisite study.
Open access · goldAbstract readMulticenter Study
In one paragraph
Article in Annals of clinical and translational neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 7% of its field
What it found
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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.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Neuropsychological Profiles in Genetic Frontotemporal Dementia: A Meta-Analysis and Systematic Review.Aging and disease · 2024Pooled it
- Genetic frontotemporal degeneration across the lifespan? A critical appraisal of the neurodevelopmental hypothesis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Neurodevelopmental origins of age-related neurodegenerative diseases.EBioMedicine · 2026Review
- Tau filaments with the Alzheimer fold in human MAPT mutants V337M and R406W.Nature structural & molecular biology · 2025Article
- Structural and functional connectivity in tau mutation carriers: from presymptomatic to symptomatic frontotemporal dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Clinical and neuroimaging characterization of the first frontotemporal dementia family carrying the MAPT p.K298E mutation.Neurogenetics · 2024Article
- Tau filaments with the Alzheimer fold in cases withbioRxiv : the preprint server for biology · 2024Article
- Novel avenues of tau research.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- Neurite-based white matter alterations in MAPT mutation carriers: A multi-shell diffusion MRI study in the ALLFTD consortium.Neurobiology of aging · 2024Article
- Assessing network degeneration and phenotypic heterogeneity in genetic frontotemporal lobar degeneration by decoding FDG-PET.NeuroImage. Clinical · 2024Article
- Longitudinal changes in qualitative aspects of semantic fluency in presymptomatic and prodromal genetic frontotemporal dementia.Journal of neurology · 2023Article
- Network Connectivity Alterations across the MAPT Mutation Clinical Spectrum.Annals of neurology · 2023Article
- Detection of Alzheimer's disease onset using MRI and PET neuroimaging: longitudinal data analysis and machine learning.Neural regeneration research · 2023Review
- Presymptomatic and early pathological features of MAPT-associated frontotemporal lobar degeneration.Acta neuropathologica communications · 2023Article
- Patients carrying the mutation p.R406W in MAPT present with non-conforming phenotypic spectrum.Brain : a journal of neurology · 2023Article
- Neurocognitive patterns across genetic levels in behavioral variant frontotemporal dementia: a multiple single cases study.BMC neurology · 2022Article
- Isoform-specific patterns of tau burden and neuronal degeneration in MAPT-associated frontotemporal lobar degeneration.Acta neuropathologica · 2022Article
- Genetic map of regional sulcal morphology in the human brain from UK biobank data.Nature communications · 2022Article
- Temporal order of clinical and biomarker changes in familial frontotemporal dementia.Nature medicine · 2022Article
- Reconfigured metabolism brain network in asymptomatic microtubule-associated protein tau mutation carriers: a graph theoretical analysis.Alzheimer's research & therapy · 2022Article
Corrections and comments
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Authors and funding
60 authors at 20 institutions in 4 countries.
Stephanie A ChuMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.ORCID 0000-0001-5749-2139
Taru M FlaganMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
Adam M StaffaroniMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
Lize C JiskootErasmus Medical Center, Rotterdam, Netherlands.
Jersey DengMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
Salvatore SpinaMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
Liwen ZhangMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
Virginia E SturmMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
Jennifer S YokoyamaMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
William W SeeleyMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
Janne M PapmaErasmus Medical Center, Rotterdam, Netherlands.
Dan H GeschwindUniversity of California, Los Angeles, Los Angeles, California, USA.
Howard J RosenMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
Bradley F BoeveMayo Clinic, Rochester, Minnesota, USA.
Adam L BoxerMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
Hilary W HeuerMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
Leah K ForsbergMayo Clinic, Rochester, Minnesota, USA.
Danielle E BrushaberMayo Clinic, Rochester, Minnesota, USA.
Murray GrossmanPerelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Giovanni CoppolaUniversity of California, Los Angeles, Los Angeles, California, USA.
Bradford C DickersonMassachusetts General Hospital, Boston, Massachusetts, USA.
Yvette M BordelonUniversity of California, Los Angeles, Los Angeles, California, USA.
Kelley FaberSchool of Medicine, Indiana University, Indianapolis, Indiana, USA.
Howard H FeldmanUniversity of California, San Diego, La Jolla, California, USA.
Julie A FieldsMayo Clinic, Rochester, Minnesota, USA.
Jamie C FongMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
Tatiana ForoudSchool of Medicine, Indiana University, Indianapolis, Indiana, USA.
Ralitza H GavrilovaMayo Clinic, Rochester, Minnesota, USA.
Nupur GhoshalWashington University School of Medicine, St. Louis, Missouri, USA.
Neill R Graff-RadfordMayo Clinic, Jacksonville, Florida, USA.
Ging-Yuek Robin HsiungUniversity of British Columbia, Vancouver, British Columbia, Canada.
Edward D HueyDepartments of Psychiatry and Neurology, Columbia University, New York, New York, USA.
David J IrwinUniversity of California, Los Angeles, Los Angeles, California, USA.
Kejal KantarciPerelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID 0000-0002-8001-2081
Daniel I KauferUniversity of North Carolina, Chapel Hill, North Carolina, USA.
Anna M KarydasMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
David S KnopmanMayo Clinic, Rochester, Minnesota, USA.ORCID 0000-0002-6544-066X
John KornakDepartment of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
Joel H KramerMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
Walter A KukullNational Alzheimer's Coordinating Center, University of Washington, Seattle, Washington, USA.
Maria I LapidMayo Clinic, Rochester, Minnesota, USA.
Irene LitvanUniversity of California, San Diego, La Jolla, California, USA.
Ian R A MackenzieUniversity of British Columbia, Vancouver, British Columbia, Canada.
Mario F MendezUniversity of California, Los Angeles, Los Angeles, California, USA.
Bruce L MillerMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
Chiadi U OnyikeJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Alexander Y PantelyatJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Rosa RademakersMayo Clinic, Jacksonville, Florida, USA.
Eliana Marisa RamosUniversity of California, Los Angeles, Los Angeles, California, USA.
Erik D RobersonUniversity of Alabama at Birmingham, Birmingham, Alabama, USA.
Maria Carmela TartagliaTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
Nadine A TattonThe Association for Frontotemporal Degeneration, Radnor, Pennsylvania, USA.
Arthur W TogaUSC Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, California, USA.
Ashley VetorSchool of Medicine, Indiana University, Indianapolis, Indiana, USA.
Sandra WeintraubNorthwestern Feinberg School of Medicine, Chicago, Illinois, USA.
Bonnie WongMassachusetts General Hospital, Boston, Massachusetts, USA.
Zbigniew K WszolekMayo Clinic, Jacksonville, Florida, USA.
ARTFL/LEFFTDS Consortium
John C Van SwietenErasmus Medical Center, Rotterdam, Netherlands.
Suzee E LeeMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.ORCID 0000-0002-4739-7215
University of California, San Francisco · USMayo Clinic · USUniversity of California, Los Angeles · USErasmus MC · NLIndiana University Indianapolis · USJacksonville College · USJohns Hopkins University · USMassachusetts General Hospital · USUniversity of British Columbia · CAUniversity of California San Diego · USUniversity of Pennsylvania · USAssociation for Frontotemporal Degeneration · USColumbia University · USNorthwestern University · USUniversity of Alabama at Birmingham · USUniversity of North Carolina at Chapel Hill · USUniversity of Southern California · USUniversity of Toronto · CAUniversity of Washington · USWashington University in St. Louis · US
Funding
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
$119.8MNATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8MTDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2MSatellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3MNational Alzheimer's Coordinating CenterU24AG072122 · NIA · UNIVERSITY OF WASHINGTON · PI STEPHENS, KARI A · 2021 to 2025
$45.8MResearch Education ComponentP30AG062422 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Serggio Carlo Lanata · 2019 to 2026
$36.9MResearch Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Christine S Ritchie · 2019 to 2026
$36.5MUCSD Shiley-Marcos Alzheimer's Disease Research Center P30P30AG062429 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Steven Dyal Edland · 2019 to 2026
$34.9MResearch Education CoreP30AG066462 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Andrew Franklin Teich · 2020 to 2026
$30.1MResearch Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI Corinne Pettigrew · 2020 to 2026
$29.3MNeuropathology CoreP30AG013854 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI BIGIO, EILEEN H. · 1996 to 2020
$28.9MUSCADRC Diversity Supplement PachicanoP30AG066530 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HELENA Chang CHUI, ARTHUR W TOGA · 2020 to 2026
$27.8MNIA NIH HHS K08 AG052648NIA NIH HHS K23 AG039414NIA NIH HHS K23 AG059891NIA NIH HHS K23 AG061253NIA NIH HHS K24 AG045333NIA NIH HHS L30 AG064696NIA NIH HHS P01 AG019724NIA NIH HHS P01 AG066597NIA NIH HHS P30 AG013854NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG062429NIA NIH HHS P30 AG066462NIA NIH HHS P30 AG066507NIA NIH HHS P30 AG066530NIA NIH HHS P50 AG008702NIA NIH HHS P50 AG023501NIA NIH HHS R01 AG026938NIA NIH HHS R01 AG038791NIA NIH HHS R01 AG052496NIA NIH HHS R01 AG057204NIA NIH HHS R01 AG058233NIA NIH HHS R01 AG062268NIA NIH HHS RC1 AG035610NIA NIH HHS U01 AG016976NIA NIH HHS U01 AG045390NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG072122NIA NIH HHS U24AG21886NIH HHS 2R01AG038791NIH HHS AG035610NIH HHS K23AG039414NIH HHS P01 AG019724NIH HHS P50 AG023501NIH HHS R01 AG26938NIH HHS R01 NS076837NIH HHS R35 NS097261NIH HHS U01 AG045390NIH HHS U54 NS092089NIH HHS UG3 NS103870NIMH NIH HHS R01 MH120794NINDS NIH HHS R01 NS076837NINDS NIH HHS R35 NS097261NINDS NIH HHS U54 NS092089NINDS NIH HHS UG3 NS103870NINDS NIH HHS UH3 NS103870
Abstract
objectiveMAPT mutations typically cause behavioral variant frontotemporal dementia with or without parkinsonism. Previous studies have shown that symptomatic MAPT mutation carriers have frontotemporal atrophy, yet studies have shown mixed results as to whether presymptomatic carriers have low gray matter volumes. To elucidate whether presymptomatic carriers have lower structural brain volumes within regions atrophied during the symptomatic phase, we studied a large cohort of MAPT mutation carriers using a voxelwise approach.
methodsWe studied 22 symptomatic carriers (age 54.7 ± 9.1, 13 female) and 43 presymptomatic carriers (age 39.2 ± 10.4, 21 female). Symptomatic carriers' clinical syndromes included: behavioral variant frontotemporal dementia (18), an amnestic dementia syndrome (2), Parkinson's disease (1), and mild cognitive impairment (1). We performed voxel-based morphometry on T1 images and assessed brain volumetrics by clinical subgroup, age, and mutation subtype.
resultsSymptomatic carriers showed gray matter atrophy in bilateral frontotemporal cortex, insula, and striatum, and white matter atrophy in bilateral corpus callosum and uncinate fasciculus. Approximately 20% of presymptomatic carriers had low gray matter volumes in bilateral hippocampus, amygdala, and lateral temporal cortex. Within these regions, low gray matter volumes emerged in a subset of presymptomatic carriers as early as their thirties. Low white matter volumes arose infrequently among presymptomatic carriers.
interpretationA subset of presymptomatic MAPT mutation carriers showed low volumes in mesial temporal lobe, the region ubiquitously atrophied in all symptomatic carriers. With each decade of age, an increasing percentage of presymptomatic carriers showed low mesial temporal volume, suggestive of early neurodegeneration.
Indexed as
AdultAgedBrainFemaleFrontotemporal DementiaHeterozygoteHumansMaleMiddle AgedMutationtau ProteinsMAPT protein, humantau Proteins
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