Evidence map›Paper›PMID 40541209›Full record

ArticleThe Lancet. Neurology2025

Prediction of amyloid and tau brain deposition and cognitive decline in people with Down syndrome using plasma biomarkers: a longitudinal cohort study.

Shorena Janelidze, Lyduine E Collij, Niklas Mattsson-Carlgren, Alex Antill, Charles M Laymon, Ira Lott, H Diana Rosas, Davneet S Minhas, Weiquan Luo, Shahid Zaman and 12 more

Abstract read
In one paragraph

Article in The Lancet. Neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Article
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  9. Observational
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

22 authors.

Shorena JanelidzeClinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden. Electronic address: shorena.janelidze@med.lu.se.
Lyduine E CollijClinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden; Department of Radiology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, Netherlands; Brain Imaging, Amsterdam Neuroscience, Amsterdam, Netherlands.
Niklas Mattsson-CarlgrenClinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden; Memory Clinic, Skåne University Hospital, Malmö, Sweden; Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.
Alex AntillClinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden.
Charles M LaymonDepartment of Radiology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.
Ira LottDepartment of Pediatrics, University of California, Irvine, School of Medicine, Orange, CA, USA.
H Diana RosasAthinoula A Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Davneet S MinhasDepartment of Radiology, University of Pittsburgh, Pittsburgh, PA, USA.
Weiquan LuoDepartment of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.
Shahid ZamanDepartment of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
Alzheimer's Biomarker Consortium–Down Syndrome investigators
Mark MapstoneDepartment of Neurology, University of California, Irvine, Irvine, CA, USA.
Elizabeth HeadDepartment of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, CA, USA.
Florence LaiDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Sigan L HartleyWaisman Center, University of Wisconsin-Madison, Madison, WI, USA.
Beau M AncesWashington University School of Medicine in St Louis, St Louis, MO, USA.
Sharon J Krinsky-McHaleNYS Institute for Basic Research in Developmental Disabilities, Department of Psychology, Staten Island, NY, USA.
Joseph H LeeTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Sergievsky Center, Departments of Neurology and Epidemiology, Columbia University Irving Medical Center, New York, NY, USA.
Rik OssenkoppeleClinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden; Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, Netherlands; Neurodegeneration, Amsterdam Neuroscience, Amsterdam, Netherlands.
Bradley T ChristianWaisman Center, University of Wisconsin-Madison, Madison, WI, USA.
Benjamin L HandenDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Oskar HanssonClinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden. Electronic address: oskar.hansson@med.lu.se.

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
$119.8M
Project 3: Biomarkers for DS Clinical TrialsU19AG068054 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEE, JOSEPH HYUNGWOO · 2020 to 2025
$103.7M
NIA NIH HHS U19 AG068054NIA NIH HHS U24 AG021886
6 · The paper itself

Abstract

backgroundPlasma biomarkers associated with Alzheimer's disease could improve prognostic assessment for people with Down syndrome in both clinical practice and research settings. We aimed to identify the plasma biomarkers that most accurately predict longitudinal changes in Alzheimer's disease-related pathology and cognitive functioning in individuals with Down syndrome.

methodsThis longitudinal cohort study included data from 258 adults (aged ≥25 years) with Down syndrome who were followed up prospectively every 16 months as part of the longitudinal Alzheimer's Biomarker Consortium-Down Syndrome study (recruited from seven university sites in the USA and UK between July 13, 2016, and Jan 15, 2019). Participants had baseline and longitudinal assessments of plasma tau phosphorylated at threonine 217 (p-tau217), glial fibrillary acidic protein (GFAP), amyloid β (Aβ)

findingsBaseline p-tau217, as well as GFAP, NfL, or t-tau, were individually associated with longitudinal changes in DS-MSE, Aβ-PET, and tau-PET, and with progression to dementia. However, in combined models, only baseline p-tau217 remained associated with changes in DS-MSE (β -0·30 [95% CI -0·45 to -0·15], p=0·0001, n=220), tau-PET (0·42 [0·14 to 0·70], p=0·0039, n=88), and progression to dementia (hazard ratio 3·51 [95% CI 1·76-7·00], p=0·0004, n=194), whereas baseline p-tau217 (0·29 [0·14-0·45], p=0·0003) and GFAP (0·37 [0·18-0·56], p=0·0003) were associated with changes in Aβ-PET (n=106 for both). Similar associations were shown between longitudinal p-tau217 or GFAP and changes in DS-MSE (p-tau217: β -0·33 [95% CI-0·52 to -0·13], p=0·0015, n=133), tau-PET (p-tau217: 0·61 [0·40 to 0·83], p<0·0001, n=87), and Aβ-PET (p-tau217: 0·35 [0·19 to 0·50], p<0·0001; GFAP: 0·49 [0·27 to 0·70], p<0·0001, n=88).

interpretationBaseline and longitudinal plasma p-tau217 were associated with subsequent decline in global cognition, progression to dementia, and increased tau burden, whereas baseline p-tau217 and GFAP were associated with Aβ accumulation. These findings suggest that plasma p-tau217 and GFAP might be valuable for prognostic assessment of Alzheimer's disease in people with Down syndrome in both clinical and research contexts. The results further support evaluation of these biomarkers for monitoring disease progression in clinical trials of Down syndrome-related Alzheimer's disease.

fundingThe European Research Council and National Institute on Aging (National Institute of Health).

Indexed as

Amyloid beta-PeptidesBrainCognitive DysfunctionDown Syndrometau ProteinsAdultAgedBiomarkersCohort StudiesDisease ProgressionFemaleGlial Fibrillary Acidic ProteinHumansLongitudinal StudiesMaleMiddle AgedAmyloid beta-PeptidesBiomarkersGFAP protein, humanGlial Fibrillary Acidic ProteinMAPT protein, humanneurofilament protein LNeurofilament Proteinstau Proteins

Identifiers

PMID40541209
PMCPMC12174012

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Registered trials

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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.