Evidence map›Paper›PMID 40985290›Full record

Trial reportAlzheimer's & dementia : the journal of the Alzheimer's Association2025

The relationship of soluble tau species with Alzheimer's disease amyloid plaque removal and tau pathology.

Eric M McDade, Nicolas R Barthélemy, Guoqiao Wang, Yan Li, Yuchen Cao, Brian Gordon, Tammie L S Benzinger, David Clifford, Alison M Goate, Alan E Renton and 40 more

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01760005 (A Phase II/III Multicenter Randomized, Double-Blind, Placebo-Controlled Platform Trial of Potential Disease Modifying Therapies Utilizing Biomarker, Cognitive, and Clinical Endpoints in Dominantly Inherited Alzheimer's Disease), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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.

NCT01760005 phase2 / phase3active not recruitingnot on this map

A Phase II/III Multicenter Randomized, Double-Blind, Placebo-Controlled Platform Trial of Potential Disease Modifying Therapies Utilizing Biomarker, Cognitive, and Clinical Endpoints in Dominantly Inherited Alzheimer's Disease

TypeinterventionalSponsorWashington University School of MedicineRan2012 to 2028Enrolled490ConditionsAlzheimers Disease, Dementia, Alzheimers Disease, FamilialArmsGantenerumab, Solanezumab, Matching Placebo (Gantenerumab), Matching Placebo (Solanezumab), E2814
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. The relationship of soluble tau species with Alzheimer's disease amyloid plaque removal and tau pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Trial
  2. Article
  3. Review
  4. Review
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

50 authors.

Eric M McDadeDepartment of Neurology, Washington University School of Medicine at St. Louis, St. Louis, Missouri, USA.ORCID 0000-0002-6764-3866
Nicolas R BarthélemyDepartment of Neurology, Washington University School of Medicine at St. Louis, St. Louis, Missouri, USA.
Guoqiao WangDepartment of Neurology, Washington University School of Medicine at St. Louis, St. Louis, Missouri, USA.
Yan LiDepartment of Neurology, Washington University School of Medicine at St. Louis, St. Louis, Missouri, USA.
Yuchen CaoDepartment of Neurology, Washington University School of Medicine at St. Louis, St. Louis, Missouri, USA.
Brian GordonDepartment of Neurology, Washington University School of Medicine at St. Louis, St. Louis, Missouri, USA.
Tammie L S BenzingerDepartment of Neurology, Washington University School of Medicine at St. Louis, St. Louis, Missouri, USA.
David CliffordDepartment of Neurology, Washington University School of Medicine at St. Louis, St. Louis, Missouri, USA.
Alison M GoateRonald M. Loeb Center for Alzheimer Disease, Dept of Genetics and Genomic Sciences, and Nash Family Dept of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Alan E RentonRonald M. Loeb Center for Alzheimer Disease, Dept of Genetics and Genomic Sciences, and Nash Family Dept of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Jason HassenstabDepartment of Neurology, Washington University School of Medicine at St. Louis, St. Louis, Missouri, USA.
Jorge J Llibre-GuerraDepartment of Neurology, Washington University School of Medicine at St. Louis, St. Louis, Missouri, USA.
Richard J PerrinDepartment of Neurology, Washington University School of Medicine at St. Louis, St. Louis, Missouri, USA.
Chengjie XiongDepartment of Biostatistics, Washington University School of Medicine at St. Louis, St. Louis, Missouri, USA.
Carlos CruchagaDepartment of Psychiatry, Washington University School of Medicine at St. Louis, St. Louis, Missouri, USA.
Catherine J MummeryDementia Research Centre, University College London, National Hospital for Neurology and Neurosurgery, London, UK.
Sarah B BermanDepartment of Neurology and Translational Science, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
James LahGoizueta Alzheimer Disease Research Center, Emory University, Atlanta, Georgia, USA.
Erik D RobersonDepartment of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Christopher Van DyckDepartment of Psychiatry, Neurology, and Neuroscience, Yale University School of Medicine, New Haven, Connecticut, USA.
Serge GauthierDepartment of Psychiatry, McGill Center for Studies in Aging, Montreal, Canada.
Colin L MastersFlorey Institute, The University of Melbourne, Melbourne, Australia.
Mario MasellisSunnybrook Research Institute, Toronto, Ontario, Canada.
Tobias BittnerF.Hoffmann-La Roche, Basel, Switzerland.
Roy YaariEli Lilly and Company, Indianapolis, Indiana, USA.
Jasmeer ChhatwalBrigham and Women's Hospital, Massachusetts General Hospital, Cambridge, Massachusetts, USA.
Patricio ChremFundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), Buenos Aires, Argentina.
William BrooksNeuroscience Research Australia and University of New South Wales Medicine, Sydney, Australia.
Kazushi SuzukiNational Defense Medical College, Japan Osaka City University, Osaka, Japan.
Johannes J LevinGerman Center for Neurodegenerative Diseases (DZNE), German Center for Neurodegenerative Diseases (DZNE) Munich, and University Hospital Ludwig-Maximilians-Universität (LMU) Munich, München, Bavaria, Germany.
Mathias JuckerGerman Center for Neurodegenerative Diseases (DZNE), German Center for Neurodegenerative Diseases (DZNE) Tübingen, and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Baden-Württemberg, Germany.
John RingmanDepartment of Neurology, University of Southern California, Los Angeles, California, USA.
David WallonCNR-MAJ, CHU Rouen, Rouen, France.
Takeshi IkeuchiNiigata University, Niigata, Niigata, Japan.
Jae-Hong LeeDepartment of Neurology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Jee Hoon RohAsan Medical Center, Seoul, South Korea.
Peter SchofieldNeuroscience Research Australia and University of New South Wales Medicine, Sydney, Australia.
Nick C FoxDementia Research Centre, University College London, National Hospital for Neurology and Neurosurgery, London, UK.
Natalie S RyanDementia Research Centre, University College London, National Hospital for Neurology and Neurosurgery, London, UK.
Jonathan VögleinGerman Center for Neurodegenerative Diseases (DZNE), German Center for Neurodegenerative Diseases (DZNE) Munich, and University Hospital Ludwig-Maximilians-Universität (LMU) Munich, München, Bavaria, Germany.
Celeste KarchDepartment of Psychiatry, Washington University School of Medicine at St. Louis, St. Louis, Missouri, USA.
Laura IbáñezDepartment of Neurology, Washington University School of Medicine at St. Louis, St. Louis, Missouri, USA.
Gregory S DayMayo Clinic in Florida, Jacksonville, Florida, USA.
Raquel Sánchez-ValleAlzheimer's disease and other cognitive disorders unit. Hospical Clinic de Barcelona, FRCB-IDIBAPS, University of Barcelona, Barcelona, Spain.
Alisha DanielsDepartment of Neurology, Washington University School of Medicine at St. Louis, St. Louis, Missouri, USA.
John C MorrisDepartment of Neurology, Washington University School of Medicine at St. Louis, St. Louis, Missouri, USA.
Charlene Supnet-BellDepartment of Neurology, Washington University School of Medicine at St. Louis, St. Louis, Missouri, USA.
Allan I LeveyGoizueta Alzheimer Disease Research Center, Emory University, Atlanta, Georgia, USA.
Randall J BatemanDepartment of Neurology, Washington University School of Medicine at St. Louis, St. Louis, Missouri, USA.ORCID 0000-0002-7729-1702
DIAN‐TU Study Team and DIAN Obs Team

Funding

Imaging CoreU19AG032438 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2010 to 2025
$53.9M
DIAN-TU Next Generation Prevention Trial - Data Request Management SupplementR01AG053267 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2017 to 2023
$34.9M
Research Education ComponentP30AG066444 · NIA · WASHINGTON UNIVERSITY · PI DAVID M. HOLTZMAN · 2020 to 2026
$28.7M
USCADRC Diversity Supplement PachicanoP30AG066530 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HELENA Chang CHUI, ARTHUR W TOGA · 2020 to 2026
$27.8M
Dominantly Inherited Alzheimer's Network Trials Unit - Adaptive Prevention TrialR01AG046179 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2014 to 2019
$26.6M
DOMINANTLY INHERITED ALZHEIMER NETWORK TRIAL: AN OPPORTUNITY TO PREVENT DEMENTIAU01AG042791 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2013 to 2018
$8.9M
Cerebrovascular Reactivity in the Presence of Cerebral Amyloid and Cerebrovascular Disease: A novel multi-modal imaging measure of vascular reserve in cognitively normal elderlyK23AG046363 · NIA · WASHINGTON UNIVERSITY · PI MCDADE, ERIC MARTIN · 2015 to 2019
$677k
Alzheimer's Association AARF-16-443265Alzheimer's Association DIAN-TTU-12-243040Alzheimer's Association SG-20-690363-DIANAnonymous organizationAvid RadiopharmaceuticalsBrain Canada FoundationCanadian Consortium of Neurodegeneration and AgingCIHRCogstate (in-kind)Eisai IncorporatedEli Lilly and CompanyF. Hoffmann-La Roche Ltd.Fonds de Recherche du Québec - SantéGerman Center for Neurodegenerative DiseasesGHR FoundationJapan Agency for Medical Research and DevelopmentKorea Health Technology R&D Project, Korea Health Industry Development Institute (KHIDI)Korea Health Industry Development Institute (KHIDI)NIA NIH HHS K23 AG046363NIA NIH HHS K23AG046363NIA NIH HHS P30 AG066444NIA NIH HHS P30AG066444(pilot35.3)NIA NIH HHS P30 AG066530NIA NIH HHS R01 AG046179NIA NIH HHS R01AG046179NIA NIH HHS R01 AG053267NIA NIH HHS R01AG053267-S1NIA NIH HHS U01 AG042791NIA NIH HHS U01AG042791NIA NIH HHS U01AG042791-S1NIA NIH HHS U19 AG032438NIA NIH HHS U19AG032438Raul Carrea Institute for Neurological Research (FLENI)Signant Health (in-kind)Spanish Institute of Health Carlos III
6 · The paper itself

Abstract

backgroundTau-derived cerebrospinal fluid (CSF) biomarkers correlate with amyloid-beta (Aβ) plaques or tau tangles in Alzheimer's disease (AD). This study assessed the effects of long-term anti-Aβ antibodies on amyloid plaques, tau tangles, and CSF tau species to determine the relationships between them.

methodsA post-hoc analysis of the DIAN-TU-001 trial (NCT01760005) examined 142 participants at risk for dominantly inherited AD randomized to solanezumab (n = 50), gantenerumab (n = 52), or placebo (n = 40). High-resolution mass spectrometry quantified CSF tau species over four years.

resultsPhosphorylated tau (p-tau) species (153, 181, 217, 231) increased early in preclinical AD but were reduced with gantenerumab-mediated Aβ plaque reduction. Nearly a decade later, MTBR-tau243 and p-tau205 increased, showing no association with Aβ reduction, aligning with tau tangle pathology progression. DISCUSSION: Initially changing soluble p-tau species track Aβ plaque reduction, while ptau205 and MTBR-243 reflect tau tangle pathology, informing different pathways of therapeutic strategies. HIGHLIGHTS: p-tau217 and p-tau231 correlate with Aβ-PET and respond to Aβ-plaque lowering therapies. Aβ immunotherapy trials support a direct link between p-tau changes and Aβ plaques Gantenerumab reduces Aβ plaques but does not affect tau NFT-related biomarkers. Blood-based p-tau217 assays may provide a non-invasive tool to monitor Aβ therapies. MTBR-tau243 strongly correlates with tau PET and tracks NFT pathology progression. Further studies are needed to validate tau biomarkers for tracking NFT-targeting therapies.

Indexed as

Alzheimer DiseaseAntibodies, Monoclonal, HumanizedPlaque, Amyloidtau ProteinsAgedAmyloid beta-PeptidesBiomarkersFemaleHumansMaleMiddle AgedPhosphorylationAmyloid beta-PeptidesAntibodies, Monoclonal, HumanizedBiomarkersgantenerumabsolanezumabtau Proteinsamyloid beta plaque reductiondominantly inherited Alzheimer's diseasemicrotubule‐binding regionphosphorylated tau

Identifiers

PMID40985290
PMCPMC12455363

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Registered trials

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.