Evidence mapPaperPMID 41814022Full record

ArticleNature aging2026

Microglia protein profiles in CSF across Alzheimer's disease clinical stages.

Elena-Raluca Blujdea, Pieter van Bokhoven, Pamela V Martino-Adami, Victoria S Marshe, Ellen M Vromen, Yanaika S Hok-A-Hin, Walter A Boiten, David J Irwin, Alice S Chen-Plotkin, Afina W Lemstra and 23 more

Abstract read
In one paragraph

Article in Nature aging, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

33 authors.

Elena-Raluca BlujdeaNeurochemistry Laboratory and Biobank, Department of Laboratory Medicine, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. e.blujdea@amsterdamumc.nl.ORCID http://orcid.org/0009-0001-7305-2122
Pieter van BokhovenCandidate Center, Neurology, Amsterdam Neuroscience, Amsterdam UMC, Amsterdam, The Netherlands.
Pamela V Martino-AdamiDivision of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.ORCID http://orcid.org/0000-0002-1067-1495
Victoria S MarsheCenter for Translational & Computational Neuroimmunology, Neuroimmunology Division, Department of Neurology and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA.
Ellen M VromenAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Yanaika S Hok-A-HinNeurochemistry Laboratory and Biobank, Department of Laboratory Medicine, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0001-9713-116X
Walter A BoitenNeurochemistry Laboratory and Biobank, Department of Laboratory Medicine, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
David J IrwinDepartment of Neurology and Penn Frontotemporal Degeneration Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-5599-5098
Alice S Chen-PlotkinDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-3387-2038
Afina W LemstraAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Yolande PijnenburgAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Wiesje M van der FlierAlzheimer Nederland, Amersfoort, The Netherlands.ORCID http://orcid.org/0000-0001-8766-6224
Oliver PetersGerman Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.ORCID http://orcid.org/0000-0003-0568-2998
Julian Hellmann-RegenGerman Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
Josef PrillerGerman Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.ORCID http://orcid.org/0000-0001-7596-0979
Anja SchneiderGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.ORCID http://orcid.org/0000-0001-9540-8700
Jens WiltfangGerman Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany.ORCID http://orcid.org/0000-0003-1492-5330
Frank JessenGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Emrah DüzelGerman Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
Katharina BuergerGerman Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Robert PerneczkyGerman Center for Neurodegenerative Diseases (DZNE), Munich, Germany.ORCID http://orcid.org/0000-0003-1981-7435
Stefan TeipelGerman Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.
Christoph LaskeGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Frederic BrosseronGerman Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.ORCID http://orcid.org/0000-0003-3137-7516
DELCODE Consortium
Marta Del CampoBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.ORCID http://orcid.org/0000-0003-2808-3699
Ruud WijdevenAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Pieter-Jelle VisserDepartment of Radiology and Nuclear Medicine, Amsterdam UMC, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0001-8008-9727
Betty M TijmsAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-2612-1797
Philip L De JagerCenter for Translational & Computational Neuroimmunology, Neuroimmunology Division, Department of Neurology and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-8057-2505
Alfredo RamirezDivision of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.ORCID http://orcid.org/0000-0003-4991-763X
Charlotte E TeunissenNeurochemistry Laboratory and Biobank, Department of Laboratory Medicine, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-4061-0837
Lisa VermuntNeurochemistry Laboratory and Biobank, Department of Laboratory Medicine, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0001-7420-6384

Funding

Project IV: In Vivo Dissection of Genetic Modifiers on Different Stages of SynucleinopathyP01AG084497 · UNIVERSITY OF PENNSYLVANIA · 2025 to 2025
$3.7M
Understanding biomarkers of cognitive decline in Lewy body diseasesR37NS115139 · UNIVERSITY OF PENNSYLVANIA · 2025 to 2025
$758k
Alzheimer Nederland (Alzheimer Netherlands) WE.03-2018-05NIA NIH HHS P01 AG084497NINDS NIH HHS R37 NS115139
6 · The paper itself

Abstract

Microglia are implicated in the progression of Alzheimer's disease (AD) pathology from its earliest stages, suggesting that cerebrospinal fluid (CSF) microglia profiling across clinical AD stages can aid in treatment development and monitoring. We analyzed two CSF cohorts (n = 834) that span from unimpaired controls to preclinical and dementia AD stages, identifying 109 dysregulated microglia-related proteins. Enrichment analyses revealed innate immune processes and cellular recruitment in preclinical AD, whereas AD dementia revealed adaptive immunity and macrophage responses. Next, we aligned the in vivo microglia protein profiles with ex vivo-derived microglial transcriptomic signatures, such as disease-associated microglia phenotypes. Transcriptomic signatures were not specific to either clinical stage but spanned both. We classified an 18-protein panel highlighting distinct changes between the preclinical and dementia stages. Our findings underscore the potential of microglia-based biomarker research for AD staging, offering insights into microglia dynamics in clinical AD stages and how transcriptomic signatures translate to proteomic profiles.

Indexed as

Alzheimer DiseaseMicrogliaAgedAged, 80 and overBiomarkersDisease ProgressionFemaleHumansMaleProteomicsTranscriptomeBiomarkers

Identifiers

PMID41814022
PMCPMC13004678

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.