Evidence map›Paper›PMID 41014048›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Alzheimer's disease diagnostic progression is associated with cerebrovascular disease and neuroinflammation in adults with Down syndrome.

Natalie C Edwards, Patrick J Lao, Mohamad J Alshikho, Olivia M Ericsson, Batool Rizvi, Melissa E Petersen, Sid O'Bryant, Lisi Flores-Aguilar, Sabrina Simoes, Mark Mapstone and 16 more

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Article 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. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Use of anti-amyloid-β monoclonal antibodies in persons with Down syndrome Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
  2. Vascular contribution to cognitive impairment and dementia (VCID): proceedings of 2025 workshop of the Jackson Laboratory.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
    Article
  3. Review
  4. Article
  5. 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

26 authors.

Natalie C EdwardsTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York City, New York, USA.
Patrick J LaoTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York City, New York, USA.
Mohamad J AlshikhoTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York City, New York, USA.
Olivia M EricssonTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York City, New York, USA.
Batool RizviDepartment of Neurobiology & Behavior, University of California, Irvine, California, USA.
Melissa E PetersenUniversity of North Texas Health Science Center, Fort Worth, Texas, USA.
Sid O'BryantUniversity of North Texas Health Science Center, Fort Worth, Texas, USA.
Lisi Flores-AguilarDepartment of Pathology and Laboratory Medicine, University of California Irvine School of Medicine, University of California, Irvine, California, USA.
Sabrina SimoesTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York City, New York, USA.
Mark MapstoneDepartment of Neurology, University of California, Irvine, California, USA.
Dana L TudorascuDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Shorena JanelidzeDepartment of Clinical Sciences Malmö, Clinical Memory Research Unit, Lund University, Lund, Sweden.
Oskar HanssonDepartment of Clinical Sciences Malmö, Clinical Memory Research Unit, Lund University, Lund, Sweden.
Benjamin L HandenDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Bradley T ChristianWaisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Joseph H LeeTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York City, New York, USA.
Florence LaiDepartment of Neurology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA.
H Diana RosasDepartment of Neurology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA.
Shahid ZamanDepartment of Psychiatry, University of Cambridge, Cambridge, UK.
Ira T LottDepartment of Pediatrics and Neurology, School of Medicine, University of California, Irvine, California, USA.
Michael A YassaDepartment of Neurobiology & Behavior, University of California, Irvine, California, USA.
Alzheimer's Biomarkers Consortium–Down Syndrome (ABC‐DS) Investigators
José GutierrezDepartment of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York City, New York, USA.
Donna M WilcockStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Elizabeth HeadDepartment of Pathology and Laboratory Medicine, University of California Irvine School of Medicine, University of California, Irvine, California, USA.
Adam M BrickmanTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York City, New York, USA.

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 CHRISTIAN, BRADLEY T, HANDEN, BENJAMIN 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
TREATMENT OF DEPRESSION IN ALZHEIMER'S DISEASEP50AG005133 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SWEET, ROBERT A · 1985 to 2019
$43.0M
Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Alberto Serrano-Pozo · 2019 to 2026
$36.5M
University of California Health Participation in the National COVID Cohort Collaborative (N3C)UL1TR001414 · NCATS · UNIVERSITY OF CALIFORNIA-IRVINE · PI COOPER, DAN M, VILAIN, ERIC J. · 2015 to 2023
$35.1M
Wisconsin Alzheimer's Disease Research CenterP30AG062715 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Sanjay Asthana · 2019 to 2026
$34.5M
DS-Connect (The Down Syndrome Registry) supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)National Centralized Repository for Alzheimer's Disease and Related Dementias U24 AG21886National Institutes of Health programs: The Alzheimer's Disease Research Centers program P50 AG16537NCATS NIH HHS UL1 TR001414NCATS NIH HHS UL1 TR001857NCATS NIH HHS UL1 TR001873NCATS NIH HHS UL1 TR002345NCATS NIH HHS UL1 TR002373NIA NIH HHS F31 AG090091NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062715NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066462NIA NIH HHS P30 AG066519NIA NIH HHS P50 AG005133NIA NIH HHS P50 AG005681NIA NIH HHS P50 AG008702NIA NIH HHS RF1 AG079519NIA NIH HHS U01 AG051406NIA NIH HHS U01 AG051412NIA NIH HHS U19 AG068054NIA NIH HHS U24 AG021886NICHD NIH HHS P50 HD105353NICHD NIH HHS U54 HD087011NICHD NIH HHS U54 HD090256NIHR Cambridge Biomedical Research Centre and the Windsor Research Unit, CPFT, Fulbourn Hospital Cambridge
6 · The paper itself

Abstract

introductionDespite having few vascular risk factors, people with Down syndrome (DS) have MRI evidence of cerebrovascular disease (CVD) and neuroinflammation that worsens with Alzheimer's disease (AD) severity. We investigated whether markers of CVD and inflammation are associated with AD-related diagnostic progression in people with DS.

methodsWe included 149 participants (mean age [SD] = 44.6 [9]) from the Alzheimer's Biomarkers Consortium-Down Syndrome who had two (n = 24) or three follow-up visits (n = 125). We derived white matter hyperintensity (WMH) volume and plasma biomarker (glial fibrillary acidic protein [GFAP], amyloid beta [Aβ]42/Aβ40, hyperphosphorylated tau-217 [p-tau217], and neurofilament light [NfL]) concentrations at baseline and examined their association with progression in clinical diagnosis.

resultsHigher baseline WMH volume and higher GFAP were associated with a greater likelihood of diagnostic progression. Combining WMH and GFAP with p-tau217 improved clinical conversion classification accuracy over AD biomarkers alone. Among individuals with evidence of amyloidosis, both WMH and GFAP were associated with clinical progression. DISCUSSION: In DS, markers of CVD and inflammation are independently and synergistically associated with clinical AD progression. HIGHLIGHTS: Higher baseline white matter hyperintensity (WMH) volume and plasma glial fibrillary acidic protein (GFAP) concentration were associated with a higher likelihood of progressing from cognitively stable to either mild cognitive impairment or clinical Alzheimer's disease in Down syndrome. WMH volume and GFAP concentration discriminated between those who progressed and those who did not. Models including the independent and interactive effects of WMH and GFAP more accurately discriminated between participants who progressed diagnostically from those who did not. Individuals with evidence of amyloid pathology were more likely to progress if they also had elevated WMH or GFAP.

Indexed as

Alzheimer DiseaseCerebrovascular DisordersDown SyndromeNeuroinflammatory DiseasesAdultAmyloid beta-PeptidesBiomarkersDisease ProgressionFemaleGlial Fibrillary Acidic ProteinHumansMagnetic Resonance ImagingMaleMiddle AgedNeurofilament Proteinstau ProteinsAmyloid beta-PeptidesBiomarkersGlial Fibrillary Acidic ProteinNeurofilament Proteinstau ProteinsAlzheimer's disease progressionbiomarkerdementiawhite matter hyperintensity

Identifiers

PMID41014048
PMCPMC12475832

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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.