Evidence map›Paper›PMID 41865347›Full record

ArticleActa neuropathologica2026

Neuropathological measures of increased tau phosphorylation across the Down syndrome lifespan.

Jesse R Pascual, Isabel Rivera, Halyma Nguyen, Phong T Ngo, Alan Hoang, Elizabeth J Andrews, Jeremy Rouanet, Sierra T Wright, Lorena Sordo, Julia Kofler and 17 more

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Article in Acta neuropathologica, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

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3 · Its place in the literature

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No citing paper in PubMed yet.

4 · The record

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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

27 authors.

Jesse R PascualDepartment of Pathology and Laboratory Medicine, 1111 Gillespie Neuroscience Research Facility, University of California, Irvine, CA, 92697, USA.
Isabel RiveraDepartment of Pathology and Laboratory Medicine, 1111 Gillespie Neuroscience Research Facility, University of California, Irvine, CA, 92697, USA.
Halyma NguyenDepartment of Pathology and Laboratory Medicine, 1111 Gillespie Neuroscience Research Facility, University of California, Irvine, CA, 92697, USA.
Phong T NgoDepartment of Pathology and Laboratory Medicine, 1111 Gillespie Neuroscience Research Facility, University of California, Irvine, CA, 92697, USA.
Alan HoangDepartment of Pathology and Laboratory Medicine, 1111 Gillespie Neuroscience Research Facility, University of California, Irvine, CA, 92697, USA.
Elizabeth J AndrewsDepartment of Pathology and Laboratory Medicine, 1111 Gillespie Neuroscience Research Facility, University of California, Irvine, CA, 92697, USA.
Jeremy RouanetDepartment of Pathology and Laboratory Medicine, 1111 Gillespie Neuroscience Research Facility, University of California, Irvine, CA, 92697, USA.
Sierra T WrightDepartment of Pathology and Laboratory Medicine, 1111 Gillespie Neuroscience Research Facility, University of California, Irvine, CA, 92697, USA.
Lorena SordoDepartment of Pathology and Laboratory Medicine, 1111 Gillespie Neuroscience Research Facility, University of California, Irvine, CA, 92697, USA.
Julia KoflerDepartment of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Milos D IkonomovicDepartment of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Florence LaiDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Mark MapstoneDepartment of Neurology, University of California, Irvine, Irvine, CA, USA.
Bradley T ChristianDepartments of Medical Physics and Psychiatry, Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
Benjamin L HandenDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Ira T LottDepartment of Pediatrics, University of California, Irvine, CA, USA.
Eric DoranDepartment of Pediatrics, University of California, Irvine, CA, USA.
Christy L HomDepartment of Psychiatry and Human Behavior, University of California, Irvine, CA, USA.
Jordan HarpDepartment of Neurology, University of Kentucky, Lexington, KY, USA.
Frederick SchmittDepartment of Neurology, University of Kentucky, Lexington, KY, USA.
Dana L TudorascuDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Beau M AncesDepartment of Neurology, Washington University School of Medicine, St Louis, MO, USA.
Michael PhelanDepartment of Pathology and Laboratory Medicine, 1111 Gillespie Neuroscience Research Facility, University of California, Irvine, CA, 92697, USA.
Lei LiuBrigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Lisi Flores-AguilarDepartment of Pathology and Laboratory Medicine, 1111 Gillespie Neuroscience Research Facility, University of California, Irvine, CA, 92697, USA.
Elizabeth HeadDepartment of Pathology and Laboratory Medicine, 1111 Gillespie Neuroscience Research Facility, University of California, Irvine, CA, 92697, USA. heade@uci.edu.
Alzheimer’s Biomarkers Consortium–Down Syndrome (ABC-DS) Investigators

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 LEE, JOSEPH HYUNGWOO · 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
NCATS 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 P30 AG062421NIA NIH HHS P30 AG062715NIA NIH HHS P30 AG066468NIA NIH HHS P30 AG066519NIA NIH HHS P30 AG072946NIA NIH HHS P30 AG072973NIA NIH HHS P50 AG005133NIA NIH HHS P50 AG005681NIA NIH HHS P50 AG008702NIA NIH HHS P50 AG016573NIA NIH HHS U01 AG051406NIA NIH HHS U01 AG051412NIA NIH HHS U19 AG068054NIA NIH HHS U24 AG021886NICHD NIH HHS P50 HD105353NICHD NIH HHS R01 HD064993
6 · The paper itself

Abstract

Individuals with Down syndrome (DS) have an increased risk of developing Alzheimer disease (AD), with nearly all individuals exhibiting AD neuropathology, including amyloid beta (Aβ) plaques and neurofibrillary tangles (NFT), by age 40 years. Fluid AD biomarker studies highlight an increase in several phosphorylated tau (p-tau) epitopes in DS. However, neuropathological measures of p-tau epitopes in DS have not been examined. Therefore, our main objective was to characterize p-tau epitope burdens across the DS lifespan at autopsy. We analyzed postmortem brain samples of 98 individuals with late-onset AD (LOAD), DS with AD neuropathology (DSAD), young DS (below 40 years of age), and age-matched neurotypical controls, ranging from 1 to 96 years of age. Immunohistochemical and digital pathology measures of p-tau epitopes at threonine 181 (pThr181), threonine 217 (pThr217), and threonine 231 (pThr231) burdens in the frontal cortex were compared across groups. We observed similar pThr181, pThr217, and pThr231 burdens between DSAD and LOAD, despite DSAD cases being younger on average. Observed pThr181, pThr217, and pThr231 burdens were higher in DSAD compared to young DS and neurotypical controls. Generalized additive models (GAMs) were used to model the cross-sectional trajectory of p-tau epitope burdens across the DS lifespan. Estimated age breakpoints revealed a significant rise in frontal cortex pThr231 at age 40, followed by pThr181 and pThr217 at age 42. In summary, our findings revealed an age-associated increase in p-tau epitopes across the DS lifespan. Our results have the potential to inform future associations between neuropathological and biofluid and neuroimaging biomarker measures of p-tau epitopes.

Indexed as

Alzheimer DiseaseBrainDown Syndrometau ProteinsAdolescentAdultAgedAged, 80 and overChildChild, PreschoolFemaleHumansInfantMaleMiddle AgedNeurofibrillary TanglesMAPT protein, humantau ProteinsAlzheimer diseasePostmortempThr181pThr217pThr231Trisomy 21

Identifiers

PMID41865347
PMCPMC13006465

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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.