Evidence map›Paper›PMID 41240365›Full record

ArticleBrain : a journal of neurology2026

The tau biomarker cascade is condensed in Down syndrome compared with sporadic Alzheimer's disease.

Matthew D Zammit, Hailey Bruzzone, Karly A Cody, Jacob Morse, Rachael Wilson, Brecca T Bettcher, Max J McLachlan, Andrew K McVea, Alexandra H DiFilippo, Finnuella J Carey and 25 more

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

Article in Brain : a journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the 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.

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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Evaluation of [Acta neuropathologica communications · 2026
    Article
  4. Longitudinal amyloid burden with combined [Imaging neuroscience (Cambridge, Mass.)
    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

35 authors.

Matthew D ZammitWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA.ORCID 0000-0001-8966-8397
Hailey BruzzoneWisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
Karly A CodyWisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.ORCID 0000-0001-5996-2560
Jacob MorseWisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
Rachael WilsonWisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
Brecca T BettcherWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA.
Max J McLachlanWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA.
Andrew K McVeaWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA.
Alexandra H DiFilippoWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA.
Finnuella J CareyWisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
Shorena JanelidzeClinical Memory Research Unit, Lund University, Lund 221 00, Sweden.
Oskar HanssonClinical Memory Research Unit, Lund University, Lund 221 00, Sweden.ORCID 0000-0001-8467-7286
Julie C PriceDepartment of Radiology, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA.
Charles M LaymonDepartment of Radiology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Davneet S MinhasDepartment of Radiology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Weiquan LuoDepartment of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15260, USA.
H Diana RosasDepartment of Neurology, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA.
Florence LaiDepartment of Neurology, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA.
Joseph H LeeG. H. Sergievsky Center, Department of Neurology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Patrick J LaoG. H. Sergievsky Center, Department of Neurology, Columbia University Irving Medical Center, New York, NY 10032, USA.ORCID 0000-0003-2243-3547
Beau M AncesDepartment of Neurology, Washington University in St. Louis, St. Louis, MO 63130, USA.
Sharon J Krinsky-McHaleDepartment of Psychology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA.
Christy L HomDepartment of Psychiatry and Human Behavior, University of California Irvine School of Medicine, Orange, CA 92617, USA.
Sigan L HartleyWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA.
Shahid H ZamanCambridge Intellectual and Developmental Disabilities Research Group, University of Cambridge, Cambridge CB2 1TN, UK.
Sterling C JohnsonWisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
Ann D CohenDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Elizabeth HeadDepartment of Pathology and Laboratory Medicine, University of California Irvine, Irvine, CA 92617, USA.ORCID 0000-0003-1115-6396
Mark E MapstoneDepartment of Neurology, Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92617, USA.
Benjamin L HandenDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Bradley T ChristianWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA.
Dana L TudorascuDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Rebecca E LanghoughWisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
Tobey J BetthauserWisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.ORCID 0000-0001-8856-1352
Alzheimer Biomarker Consortium–Down Syndrome

Funding

University of Pittsburgh Clinical and Translational Science InstituteUL1TR001857 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2016 to 2025
$129.3M
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
Project 3: Biomarkers for DS Clinical TrialsU19AG068054 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TUDORASCU, DANA L · 2020 to 2025
$103.7M
Clinical and Translational Science AwardUL1TR001873 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI REILLY, MUREDACH P · 2016 to 2025
$99.0M
WU INSTITUTE OF CLINICAL AND TRANSLATIONAL SCIENCESUL1TR002345 · NCATS · WASHINGTON UNIVERSITY · PI William G. Powderly · 2017 to 2026
$97.8M
University of Wisconsin Institute for Clinical and Translational ResearchUL1TR002373 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI ELIZABETH S BURNSIDE, Allan R. Brasier · 2017 to 2026
$75.9M
WASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 1985 to 2019
$52.1M
Satellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3M
RADx-UP: Improving the Response of Local Urban and Rural Communities to Disparities in Covid-19 TestingUL1TR002366 · NCATS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Mario Castro, JAMES STEVEN LEEDER · 2017 to 2026
$44.3M
TREATMENT OF DEPRESSION IN ALZHEIMER'S DISEASEP50AG005133 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SWEET, ROBERT A · 1985 to 2019
$43.0M
UC Irvine Alzheimer's Disease Research Center Induced Pluripotent Stem Cell CoreP50AG016573 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI YASSA, MICHAEL A · 2000 to 2019
$37.0M
Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Christine S Ritchie · 2019 to 2026
$36.5M
Alzheimer Biomarkers Consortium-Down SyndromeCPFTFulbourn Hospital, Cambridge R01AG080766National Centralized Repository for Alzheimer Disease and Related Dementias U24 AG21886National Institutes of Health ProgramsNCATS NIH HHS UL1 TR001414NCATS NIH HHS UL1 TR001857NCATS NIH HHS UL1 TR001873NCATS NIH HHS UL1 TR002345NCATS NIH HHS UL1 TR002366NCATS NIH HHS UL1 TR002373NIA NIH HHS 1RF1AG094739NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062715NIA NIH HHS P30 AG066462NIA NIH HHS P30 AG066468NIA NIH HHS P30 AG066519NIA NIH HHS P30 AG072973NIA NIH HHS P50 AG005133NIA NIH HHS P50 AG005681NIA NIH HHS P50 AG008702NIA NIH HHS P50 AG016573NIA NIH HHS R01 AG080766NIA NIH HHS RF1 AG094739NIA NIH HHS U01 AG051406NIA NIH HHS U01 AG051412NIA NIH HHS U19 AG068054NIA NIH HHS U24 AG021886NICHD NIH HHS P50 HD105353NIH HHS S10 OD030415NIHR Cambridge Biomedical Research CentreODCDC CDC HHS S10 OD030415The Alzheimer's Disease Research Centers Program P50 AG16573Windsor Research Unit
6 · The paper itself

Abstract

Characterizing the timing and progression of Alzheimer's disease biomarker onset in Down syndrome (DS) and contrasting potential timing differences with neurotypical adults is needed to identify optimal Alzheimer's disease therapeutic treatment windows in DS. In this study, 198 adults with DS from the Alzheimer Biomarker Consortium-Down Syndrome and 172 neurotypical adults from the Wisconsin Registry for Alzheimer's Prevention with available longitudinal beta-amyloid PET, tau PET and plasma p-tau217 analysed on the Lilly Meso Scale Delivery Platform were included. Individuals with DS had a significantly higher lifetime risk of beta-amyloid plaque onset. Temporal modelling of longitudinal biomarker measures revealed earlier age at positivity of beta-amyloid plaques, p-tau217 and neurofibrillary tau tangles in DS relative to the neurotypical cohort. The onset of p-tau217 and tau PET positivity in DS occurred nearly simultaneously, roughly 4-6 years following beta-amyloid onset, whereas the neurotypical group displayed greater temporal latency between positivity of the two biomarkers. The early and simultaneous onset of these biomarkers in DS highlights the necessity for early therapeutic interventions in this population. This work, combined with the upcoming anti-amyloid safety and efficacy clinical trials for DS will help to identify optimal treatment windows for these individuals.

Indexed as

Alzheimer DiseaseDown Syndrometau ProteinsAdultAgedAmyloid beta-PeptidesBiomarkersDisease ProgressionFemaleHumansLongitudinal StudiesMaleMiddle AgedPlaque, AmyloidPositron-Emission TomographyAmyloid beta-PeptidesBiomarkerstau Proteinsamyloid PETbiomarker modellingDown syndromep-tau217tau PET

Identifiers

PMID41240365
PMCPMC12983235

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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.